AXSM - NASDAQ

Good morning and welcome to the Axsome Therapeutics, Inc. Fourth Quarter and Full Year 2025 Earnings Conference Call. My name is Kevin, and I will be your operator for today's call. At this time, participants are in a listen-only mode. Later, there will be a question-and-answer session, and instructions will be given at that time. Please note this call is being recorded. I would now like to hand the call over to Ashley Dongdress of Investor Relations. Ashley, please go ahead. Thank you.

Good morning, and thank you all for joining Axsome Therapeutics, Inc.’s fourth quarter and full year 2025 earnings conference call. With us today are Dr. Herriot Tabuteau, our Chief Executive Officer, Nick Pizzie, our Chief Financial Officer, and Ari Maizel, our Chief Commercial Officer. We will begin our call with prepared remarks. Mark Jacobson, our Chief Operating Officer, and Hunter Murdock, our General Counsel, will also be available for Q&A. Before we begin, I encourage everyone to visit the Investors section of our website to find the press release and presentation for today's call. Please note that today's discussion includes forward-looking statements regarding our financial performance, commercial strategy, and operational plans, including research, development, and activities. These statements are based on current expectations and assumptions and are subject to risks and uncertainties that may cause actual results to differ materially. Please refer to our SEC filings, including our quarterly and annual reports, for a description of these and other risks. You are cautioned not to rely on these forward-looking statements, which are made only as of today. The company disclaims any obligation to update such statements. And with that, I will hand it over to Herriot. Thank you, Ashley, and good morning, everyone.

2025 was a year of significant commercial, research, and development progress at Axsome. Our commercial business is strong, with Auvelity achieving sales of over $500,000,000 in its third full year of launch, Sunosi growth accelerating, and Cymbravo launching, adding a third pillar of growth. Total revenue for the fourth quarter increased 65% year over year to $196,000,000; for the full year, increased 66% to $639,000,000. Our innovative medicines continue to meaningfully improve patient outcomes. Just our current commercialized products have the potential to achieve multibillion dollars in annual peak sales. To support the continued momentum of our current products and future launches, we have built a technologically enabled scalable commercial platform. Against this backdrop, we are advancing a broad and innovative CNS pipeline, which includes five novel product candidates across nine high-impact indications. I will provide an update on our pipeline progress starting with our sNDA for Auvelity in Alzheimer's disease agitation. We recently announced the acceptance of the sNDA filing and the receipt of priority review designation with the PDUFA action date of April 30. If approved, Auvelity has the potential to address the prevalent and debilitating condition for which currently only one product is approved. As we approach the April 30 PDUFA date, launch readiness activities are underway, which Ari will discuss later in the call. We are encouraged by the level of interest within the treatment community and expect awareness to continue to build in the quarters ahead. Beyond the opportunity in Alzheimer's disease agitation, we are advancing our planned Phase III trial of AXS-05 in smoking cessation, with initiation anticipated in the second quarter. Moving to AXS-12 in narcolepsy. Following receipt of positive FDA pre-NDA meeting minutes, we have made significant progress with our NDA package, and we expect to submit that imminently. For solriamfetol, we continue to advance this differentiated molecule across multiple new indications, including ADHD, binge eating disorder, MDD with symptoms of excessive daytime sleepiness, and shift work disorder. These new indications represent significant expansion of solriamfetol's potential to help patients and create value for stakeholders. For ADHD, we recently completed a Type B meeting with the FDA, where we reached agreement on the planned Phase III studies in pediatric patients. We plan to conduct two Phase III trials in parallel, one in children and one in adolescents, and we are on track to initiate both in the first half of this year. For MDD, startup activities are underway for initiation this quarter for a Phase III trial of solriamfetol in MDD patients with symptoms of excessive daytime sleepiness. For binge eating disorder, our ENGAGE Phase III trial of solriamfetol in this indication is progressing, and we expect top-line results in the second half of this year. Finally, for solriamfetol in shift work disorder, we now anticipate top-line results in 2027, based on current enrollment trends. Turning to AXS-14. We recently initiated the FORWARD study, a Phase III double-blind, placebo-controlled, randomized withdrawal trial of AXS-14 in patients with fibromyalgia. This new study will supplement the two completed positive Phase II and Phase III trials of AXS-14 in this indication. To complement our late-stage pipeline, we recently acquired A

Thank you, Herriot, and good morning, everyone. Our fourth quarter and full year 2025 performance reflects Axsome's growing commercial portfolio and the continued advancement of our industry-leading CNS pipeline. Together, these collective achievements firmly position us for the year ahead. As Herriot mentioned, total product revenue was $196,000,000 for the fourth quarter and $638,500,000 for the year, up 65% and 66% year over year respectively, which was driven by robust Auvelity growth, the continued solid performance of Sunosi, and initial contributions from the launch of Cymbravo. Auvelity achieved net product sales of $155,100,000 for the fourth quarter, up 68% versus the prior year. Auvelity sales surpassed the $500,000,000 mark in only its third full year from launch, totaling $507,100,000, representing a 74% year over year increase. Sunosi posted another strong quarter with net product revenue of $36,700,000, a 40% increase compared to 2024. Sunosi revenue was $124,800,000 for the full year of 2025, representing a 32% increase versus last year. Cymbravo generated $4,100,000 in net sales for the fourth quarter and $6,600,000 for the full year, following its second full quarter of launch. Together, these results underscore the continued momentum of our top-line performance and disciplined execution, which is resulting in further operating leverage in the business. Auvelity and Sunosi gross-to-net discounts in 2025 were in the high-40% range. Going forward, we expect Auvelity and Sunosi gross-to-net discounts to increase to the mid-50% range due to typical Q1 dynamics. Cymbravo gross-to-net discount for the quarter was in the high-70% range, which we anticipate will remain elevated during the launch phase. Now turning to expenses. Total cost of revenue was $12,300,000 and $47,500,000 for the fourth quarter and full year of 2025 compared to $10,500,000 and $33,300,000 for the comparable periods in 2024. Research and development expenses were $48,800,000 for the fourth quarter and $183,300,000 for the full year of 2025. That is compared to $55,000,000 and $187,100,000 for the fourth quarter and full year of 2024. The decrease in R&D spend for the year was primarily driven by the completion of clinical trials for AXS-05 and solriamfetol, which was partially offset by one-time acquisition-related costs and higher costs related to AXS-07. Selling, general, and administrative expenses were $160,300,000 for the fourth quarter and $570,600,000 for the full year of 2025. That is compared to $113,300,000 and $411,400,000 for the fourth quarter and full year of 2024. The 39% increase in SG&A spend for the year was primarily driven by commercialization activities for Auvelity, including sales force expansion and the national launch of a direct-to-consumer advertising campaign, along with the commercial launch of Cymbravo. Net loss for the fourth quarter was $28,600,000, or $0.56 per share, compared to a net loss of $74,900,000, or $1.54 per share, for 2024. The $28,600,000 net loss in the quarter includes $22,700,000 in stock-based compensation expense. Net loss for the full year of 2025 was $183,200,000, or $3.68 per share, compared to a net loss of $287,200,000, or $5.99 per share, for the full year of 2024. This year's loss of $183,200,000 includes $93,800,000 of stock-based compensation expense. Now turning to the balance sheet. We ended the year with $323,000,000 in cash and cash equivalents compared to $315,000,000 at the end of 2024. Looking ahead, we continue to believe that our current cash balance is sufficient to fund anticipated operations into cash flow positivity based on our current operating plan. With that, I would like to now turn the call over to Ari, who will provide a commercial update.

Thank you, Nick. Axsome delivered strong performance in Q4 and completed 2025 with momentum for Auvelity, Cymbravo, and Sunosi. Our outstanding medicines continue to meaningfully improve patient outcomes. With our planned investments for 2026 and the power of our innovative digital-centric commercialization model, we have high confidence in our ability to deliver upon the vast opportunities that remain for our growing portfolio of CNS medicines. Beginning with Auvelity, more than 225,000 prescriptions were written in the quarter, representing 42% year over year growth and 8% sequential growth. By comparison, the antidepressant market was flat over the same time period. Our sales team continues to drive uptake across prescriber segments, particularly in the primary care setting. Primary care clinicians represented approximately one-third of all Auvelity prescribers in the quarter and continue to be the fastest growing prescriber segment, further expanding the overall prescriber base alongside continued growth within psychiatry. More than 5,300 new prescribers were activated in the quarter, bringing the total number of unique prescribers to approximately 52,000 since launch. Formulary access for Auvelity also remained strong. As of January 2026, commercial coverage increased from 75% to 78%, bringing total coverage to 86% of all lives across channels, and we expect coverage to continue to expand and evolve throughout the year. Auvelity’s growth to date reflects its distinct clinical profile, fast onset of action, sustained relief from depression symptoms, and a highly favorable safety and tolerability profile, supported by execution across our innovative commercial engine, reinforcing our confidence in the significant long-term commercial opportunity for the brand. To support the growing demand in MDD, and in anticipation of the potential launch in Alzheimer's disease agitation, we recently initiated our third and largest expansion of the Auvelity sales force to approximately 600 sales representatives. We expect to complete this expansion in the second quarter and look forward to providing additional details of these plans in the months ahead. Turning now to Cymbravo, which saw acceleration in new patient trial in Q4 resulting in more than 13,000 total prescriptions and approximately 5,300 new patients started in the quarter. Our disciplined launch strategy targeting headache specialists continues to grow advocacy for Cymbravo among the highest-volume migraine prescribers in the U.S., and we are pleased with the feedback from HCPs on the positive impact Cymbravo is having on patients. The key clinical attributes leading to Cymbravo trial include the multi-mechanistic approach to migraine symptom relief targeting multiple causes of migraine, rapid onset of action, and positive impact on patient functioning within two hours. We are excited about Cymbravo's long-term potential as a preferred acute migraine treatment. We continue to make progress with Cymbravo market access and coverage, with overall payer coverage at approximately 52% at the start of the year. The proportion of covered lives in the commercial and government channels is approximately 49% and 57% respectively. In addition, Axsome successfully contracted with a third and final large commercial GPO for Cymbravo in Q4, which now enables negotiation with all major commercial payers and PBMs. We anticipate coverage for Cymbravo to expand and evolve throughout 2026. And finally, Sunosi delivered another strong quarter of performance, with more than 54,000 prescriptions representing 11% year over year and 3% sequential growth. By comparison, the wake-promoting agent market grew 2% year over year and was flat versus Q3. Nearly 500 new clinicians prescribed Sunosi in the quarter, bringing the total cumulative prescriber base to approximately 15,100 since launch. Payer coverage for Sunosi remains steady at approximately 82% of lives covered across channels. Overall, the performance of our innovative marketed products in 2025 underlines the effectiveness of our commercial strategy and execution and positions us well as we enter 2026. Auvelity, Sunosi, and Cymbravo are delivering differentiated patient outcomes in the depression, excessive daytime sleepiness, and acute migraine markets, and together represent a proliferating growth foundation for Axsome. This year, our focus remains on scaling growth across our commercial organization and expanding adoption of our important CNS medicines. I will now turn the call back to Ashley for Q&A.

Thank you, Ari. Operator, we are ready for Q&A.

Certainly. We will now be conducting a question-and-answer session. Our first question today is coming from Leonid Timashev from RBC Capital Markets. Your line is now live.

Thanks, guys. Thanks for taking my question. I wanted to ask on what the implications are for you from the new FDA publication on sort of the one-trial policy given the amount of trials that you are running. I guess I am curious whether you think that means that some of the studies in binge eating and shift work disorder could potentially be approvable on a single Phase III. And then similarly, why, given that policy, for example, you are running two studies in ADHD splitting pediatric and adolescent patients? Thanks.

Hey, Leo. This is Mark. Good morning. So, obviously, that is hot off the press, and the team is assessing it. So one thing is, as always, we always vet our clinical plans with the FDA and their vision that the programs are under. So we are going to continue to do that. And, you know, if there are changes, we will see. You mentioned shift work disorder. That is an example where we already have alignment with FDA that the existing clinical package could serve as potential support of evidence should the study that we are conducting now be positive. So, that is one example where that is the place. I will pass it to Ari for thoughts on ADHD. But our plans for ADHD reflect, you know, regional alignment that we reached with FDA. Yeah. Yeah.

Just to add to what Mark was saying. So one thing to keep in mind is, although this is a broad guidance, each clinical situation, each indication is specific and has to be looked at from that perspective. So for ADHD, it is a disorder which affects different patient populations. For example, adults with ADHD are different from children with ADHD. So as you can imagine, this is a situation whereby you would not be able to, or the FDA would not allow you to do just one study in adults, for example. We are conducting two studies in pediatric patients with ADHD because, again, there is a sub-segmentation of pediatric patients. So you have children, so those are individuals who are less than 12 years of age, and then adolescents. So typically, the FDA does require data from both subsets of patients. It is possible, for example, to study both subsets of pediatric patients in one study. We decided to split it up into two studies, which will be conducted concurrently, and that will have no impact whatsoever on our eventual filing timeline.

Thank you. Our next question today is coming from Marc Goodman from Leerink Partners. Your line is now live.

Yes. Can you talk about AXS-17, just the types of epilepsy, the development plan that you are thinking about moving into? And you had mentioned that the product has been around and has some history in patients. Just talk about what kind of data do we have? Thank you.

Thanks for the question. So the product has been studied in different indications. So one indication that has been studied in the past is generalized anxiety disorder. And all of the safety data and safety experience comes from those studies. So it is really nice that the product has been studied in a range of doses and also with chronic dosing. As it relates to the direction of going in and looking at epilepsies, this is based on a pretty broad array of preclinical studies that have been done in epilepsy models that are predictive of clinical success. And, right now, what we are doing is we are starting—we have started—the work to make sure that we are Phase II ready and also are very closely assessing all of the various different epilepsies in which the product in preclinical models has shown promise. So stay tuned, and over the balance of this year, we will provide more details on which indication—exactly which specific epilepsy—we will target first.

Thank you. Our next question is coming from Jason Gerberry from Bank of America. Your line is now live.

Hey, guys. Thanks for taking my question. Why don’t I just follow up on the comment about Auvelity? Payer coverage evolving over the course of the year? And one thing I just wondered about, like as you add the ADA label, sometime in April, you know, should that just mirror the MDD coverage? If not, is there a process for access build post the ADA approval? And the reason I asked, you know, I think about other CNS drugs like Caplyta, right, when they added different indications, it was a pretty seamless coverage post the label add-on event. So wondering how that looks for you guys with Auvelity and the ADA indication. Thanks.

Yeah. Thanks for the question, Jason. As you stated, in general, when you have a product that is on the market for a specific indication and you expand the indication, generally speaking, your existing coverage should apply to the new indication. I think what is unique about MDD and ADA is that MDD is largely a commercial business, whereas ADA will be more weighted to Medicare Part D. Our aspiration is to get as close as possible to 100% access for the brand, and that is something that is our aspiration. So just continuing to work with plans that do not currently cover the product and continue to work on things like removing steps in PAs where they exist today.

Thank you. Our next question today is coming from Andrew Tsai from Jefferies. Your line is now live.

Hey, good morning. Thanks for the update. And back to Alzheimer's agitation, how should we think about the initial launch cadence in the first year? Do you expect your launch to be stronger than what Rexulti saw in only Alzheimer's agitation in terms of TRx volume and sales? And then maybe as a follow-up to the gross-to-net specifically, do you think combined gross-to-net for Auvelity could trend or shake out over time? Thank you.

Thanks for the question. We do not generally forecast where we would expect ultimate uptake to land. But suffice it to say, we are actively preparing for the launch to enable commercial availability and customer engagement as soon as feasible post launch. And from our perspective, there is very limited analog in the market. Obviously, there is only one other product. So we are studying that carefully as well as the MDD launch for Auvelity to really assess where we think uptake will be on the first year. You know, once we have an approval, obviously, we will share additional details about our commercial effort. And so stay tuned for some more details later in the year.

Yeah. And hey, Andrew. Just maybe a note on the GTN. So we anticipate that 70%+ scripts for ADA will be written in the Medicare Part D channel. And as such, that channel has a more favorable GTN, specifically as there is no co-pay card utilization around that. So we would expect potential favorability from where we have been on the aggregate for Auvelity.

Thank you. Our next question today is coming from Pete Stavropoulos from Cantor Fitzgerald. Your line is now live.

Good morning, and thanks for taking my questions. For Sunosi, you had double-digit year over year growth. What were the drivers of that? Is growth more volume driven, or are you seeing benefit from improved access, persistence, or share gain? And is growth being driven more by narcolepsy or OSA? Are you seeing any differences in prescriber behavior between those two segments? Thanks.

Yes. Thanks for the question, Pete. Sunosi continues to deliver steady growth in both the OSA and narcolepsy markets. As we shared before, approximately 70% of prescriptions are EDS in OSA and 30% for EDS in narcolepsy. I think over the course of the year, we saw positive growth in new patient starts, total active writers, and total prescriptions. And part of our strategy over the past couple of years has been driving depth across existing Sunosi writers. So we are seeing growth from both ends, both OSA and narcolepsy. And really across specialty or prescriber segments, including PCPs, pulmonologists, sleep specialists, and neurologists.

Thank you. Next question is coming from Graig Suvannavejh from Wells Fargo. Your line is now live.

Hey guys, this is Craig on for Ben. I appreciate the opportunity to ask a question here. I guess, could you guys provide a little bit more color on the progress of the DTC campaign? And you mentioned that Auvelity continued to grow. However, the MDD market has been overall flat. Where is that growth coming from? Are you seeing adoption in earlier lines of care? Thank you. Bye.

Yes. Thank you for the question. Yes, as you know, we launched a national TV campaign late in the year around September–October timeframe. And we have been pleased with the impact of that campaign. It did generate inflection in new patient starts. And our analysis of the impact by media channel has enabled us to optimize our spend going into 2026. So we will have more details to share on that impact as we get through the year. In terms of where the growth is coming from, you know, we are pleased with efforts to expand use in primary care while also driving continued growth in psychiatry practices. So we are seeing really nice growth across all segments. But primary care was the fastest-growing segment in Q4 in terms of new patient starts and new writers. And so we expect that to continue to be a trend as we expand our efforts in the primary care setting.

Thank you. Next question is coming from Raghuram Selvaraju from H.C. Wainwright. Your line is now live.

Thanks so much for taking my question. I was wondering if you could comment on what you expect ultimate reimbursement market access to look like for Auvelity at steady state, particularly in the context of how Sunosi percentage covered lives is around 82%. Do you expect that to be similar for Auvelity, particularly once the product is approved both across MDD and chronic agitation? Or do you expect it to go meaningfully higher? And if so, what do you expect the ultimate optimal range to look like?

Thank you. Yes. Thanks for the question. Our goal is to try to secure access for as many patients as possible across channels. And so although we do not typically guide on what the final steady-state covered lives percentage would be, I think you have seen for the past few years that we have made steady progress in terms of increasing covered lives, and our expectation is we will continue to work to ensure access for both the MDD and ADA indication.

Thank you. Our next question is coming from David A. Amsellem from Piper Sandler. Your line is now live.

Thanks. Coming back to AXS-17, and sorry if I missed any commentary here. But can you talk about how you are thinking about it beyond epilepsy? For instance, it has been about 20 years since something has been approved for generalized anxiety disorder, and given the mechanism, it would seem that could be an interesting avenue to explore. So how are you thinking about broader development of the asset? And then secondly, just in general, are you looking at other assets to bring in to further leverage your infrastructure in both neurology and psychiatry? Thank you.

Sure. As always, with any molecule, we look very carefully at the biology. With an eye to what the possibilities are in terms of potentially affecting patients positively. So we—as you know—we in-licensed the asset. Our focus right now is with regards to epilepsies. We will obviously look at other potential indications, but we want to make sure that we stay with the initial indication. We think that there is a lot of promise there in that area based on all of the preclinical work that has been done by others and also by our team. So stay tuned, and stay tuned. And I think it is a little premature to talk about add-on indications to the primary indication.

Thank you. Our next question is coming from Ashwani Verma from UBS. Your line is now live.

Hi. Thanks for taking our question. So on the salesforce expansion, pretty big step up, twice versus the 300 reps that you had before. Yeah, just curious what went into that math and if you can talk about consensus SG&A for 2026 is only showing up 15% year over year. What would be the right range for the models? Thanks.

Yes, thanks for the question, Ash. So the salesforce expansion is designed to accelerate growth in MDD, while providing scale for a potential indication approval in Alzheimer's agitation later this year. So when you think about the expansion, the national hiring of reps throughout the country to increase reach and frequency to the highest value across specialties will enable us to capitalize on the momentum that we created in the primary care segment. And primary care is growing in importance because they are frontline treaters for both MDD and ADA. And then finally, it will allow us to engage with an expanded target universe. So a larger salesforce allows us to engage with a larger group of HCP targets when you think about the specialties that will be important for both indications. Primary care, psychiatry, neurology are really the largest specialty segments that we will be focused on.

Sure. Maybe just, Ash—maybe just a minute on OpEx and 2025 to 2026. So in 2025, in the P&L, we saw revenues growing roughly 3x faster than OpEx, so significant operating leverage in 2025. Even with this expansion, with the DTC that we have done and what we plan to do in 2026, we will continue to see that operating leverage throughout the year. Obviously, Q1, Q2, we will be building that team, as you mentioned, going from 300 to 600. But this was always factored into our cash forecast. So continue to see operating leverage into 2026.

Thank you. Our next question today is coming from Ami Fadia from Needham and Company. Your line is now live.

Hi, good morning. Thanks for taking my question. My question is on Cymbravo. With the additional third commercial payer contracted in the fourth quarter, how do you see the overall coverage evolving through the course of this year? And how should we see that impacting the gross-to-net or the rate of pull-through of prescriptions as the year progresses? Thank you.

Yes. Thank you, Ami. So as we mentioned in the call, we secured a contract with the third large GPO. And as you recall, the GPO contract is really a precursor for negotiating with payers and PBMs to secure coverage. So although it does not guarantee coverage with the payers/PBM, it does allow for active negotiation. And so our team is engaged with all the national payers and PBMs. And I think we are optimistic about the potential to increase Cymbravo coverage. That is something that we are focused on primarily for this year, and we will share some additional updates as we secure access.

Maybe just a second on GTN. GTN in the quarter for Q4 was in that upper-70% range. We would anticipate that GTN to continue to remain elevated during the launch phase. And as Ari shared, as more contracts come online, you know, we believe that the GTN will be north of where Auvelity currently is, but less than GTNs that we see in the space.

Thank you. Next question is coming from Joseph Thome, TD Cowen. Your line is now live.

Hi there. Good morning. Thank you for taking my question. Maybe just in terms of the potential Alzheimer's agitation launch, when will you be in a position to be able to launch the therapy after the April 30 date? Will it take some time before we could see kind of the full-fledged launch there? And then what sort of metrics do you anticipate providing? Should the approval come through? Would you be able to separate kind of product revenues between MDD and Alzheimer's agitation? Or how can we best monitor how that specific launch is going? Thank you.

Thanks, Joseph. Yeah. We will be ready to go within a quarter on ADA. And obviously, the team right now is preparing every aspect for launch readiness. And so we are feeling really optimistic about the potential impact, if approved. And then in terms of metrics, we expect to share approximate percentage of scripts coming from the ADA space as we learn more. As you know, the typical IQVIA data does not break out by indication. And so we have not finalized our plans, but we will certainly be able to share some details about how the launch is going.

Thank you. Our next question today is coming from Sean M. Laaman from Morgan Stanley. Your line is now live.

Good morning, everyone, and hope everyone is well. Thanks for taking my question. On the pipeline, AXS-12, the NDA in narcolepsy, with the NDA submission plan for 12 in narcolepsy, how do you see differentiation versus existing therapies, particularly around cataplexy control and physician adoption? Thank you.

Yeah. Thanks for the question. As you know, narcolepsy is a challenging disease to treat, and patients often are on polypharmacy, trying to find the right combination of medications to support symptom relief. I think what is very clear is that not every patient responds to every mechanism in the same way, and there is a lot of trial and error. So from our perspective, AXS-12 offers a very compelling treatment option for patients, both in terms of cataplexy relief as well as safety and tolerability profile. And so we feel, you know, it is a novel mechanism relative to what is in the marketplace today. And based on the feedback we have received in market research, there is a high degree of interest in using this for narcolepsy patients.

Our next question is coming from Myles Robert Minter from William Blair. Your line is now live.

Hi, guys. Congrats on the year. Just on AXS-17, just wondering how you are thinking about the therapeutic window there in epilepsy. I know that A

Yeah. We are—thanks for the question—we are exploring dose. And part of that exploration is a lot of PK/PD modeling. We think that, based on the preclinical data as well as the clinical data, there is a range of potential doses. And as you mentioned, depending on exactly where you fall and which therapeutic indication, you might hit certain subsets of receptors. The goal here is to make sure that we pick a dose where we have the best risk-benefit profiles. Now the drug has not been studied previously in the clinical setting in patients with epilepsy. So, there is some work there to be done and some information to be gotten from the initial trial in those patients. So stay tuned. This is what research is about, but we are very excited about the mechanism of action and the specificity of the receptor targeting.

Thank you. Our next question is coming from Matthew Baron Hershenhorn from Oppenheimer. Your line is now live.

Hey, guys. Congrats on all the progress and thanks for taking our question. So we were thinking about the safety data for Auvelity in ADA and just wondering how you see the likely label language upon the update reflecting differentiation versus Rexulti based on what we saw in the clinical trials? And how do you think about the biggest advantages for Auvelity once both treatments are available, especially considering the safety profile in elderly patients? Really appreciate it.

Hey, Matt. Good morning. Thanks for the question. The review is underway and, by the way, just a reminder, since this is a priority review, we are more than halfway through and we are just about two months out from PDUFA. So it is a little early for us to comment on potential, you know, potential label. However, what we can share is we—you know, should the product be approved—we would expect the safety profile to be described in the label in that patient population. And we would be pleased with that. And, you know, I think that is probably as much as we can say there. And could you remind me of the second part of your question, please, or maybe, Ari, you want to field that?

Yes. Just relative to the positioning, I mean, so, obviously, when you look at our clinical data—rapid onset of action, durability of response, low side effects and safety issues, not an antipsychotic option, and currently approved as a monotherapy in MDD where there is significant comorbidity with Alzheimer's agitation—so we think that there are multiple elements of the clinical profile that will really help AXS-05 sort of stand apart. And there is a lot of excitement and enthusiasm about a potential launch amongst the Alzheimer's community.

Hey, I will take the first part of the question. Thank you for the question. Our anticipation is that AXS-12 would be a standard review. I will hand it over to Nick for the GTN.

Sure. Yeah. And correct. Based on assuming that we would see that 70%+ in the Medicare Part D channel for ADA scripts, if that is how it evolves, we would anticipate that the GTN would be more favorable. We are seeing currently in the Medicare Part D channel that it is more favorable than the commercial channel.

Thank you. Next question is coming from David Hoang from Deutsche Bank. Your line is now live.

Hi, guys. Thanks for taking my questions. So maybe just on the breakdown between the community and long-term settings for ADA. Could you remind us how that breaks down and how you are planning to deploy your salesforce to address those two segments? And then if Rexulti’s coverage should be approved for the adjacent indication of AD psychosis, do you think that could become a competitor in ADA, you know, such that if patients are being treated for AD psychosis, that might also address their agitation? Thanks a lot.

Yes. Thanks for the question, David. So as a reminder, about 60% of Alzheimer's disease agitation prescriptions are in community-based settings and 40% are in long-term care facilities. So it remains to be seen how the uptake of AXS-05 will be across those settings of care, but that is sort of how the market is behaving at the moment. And then in terms of your question on Rexulti, we do view also Alzheimer's agitation and Alzheimer's psychosis as separate and distinct indications. And so we do not expect there to be much confusion in the marketplace, and agitation symptoms are the most prominent and most burdensome for patients. And so there is significant opportunity, significant unmet treatment need, and that will be our focus at launch if approved.

Hey, sorry, I answered the question already a couple of times on MDD versus ADA. We would—we do—anticipate in that ADA channel to be more positive assuming that 70%+ would be in the Medicare Part D channel.

Yeah. It is a good question. Obviously, primary care is the dominant specialty in terms of overall volume. Because they tend to be the first-line treaters for MDD. That said, psychiatrists tend to have the greatest volume on a per-patient basis and see the most patients overall. So we have not specifically shared where we expect the final penetration to land in MDD. But as of today, we see about a third of our writer base is in primary care, whereas two-thirds is in psychiatry. Primary care has been growing as we have expanded our sales team and continue to penetrate the primary care segment. But where it will sort of end up at the end, it is difficult to say at the moment.

Thank you. Next question is coming from Graig C. Suvannavejh from Mizuho Securities. Your line is now live.

Hey, good morning. Thanks for taking my question. Congrats on the progress in the quarter and the year. My question is around the opportunity you see with AXS-12 for narcolepsy. I know there was a question earlier on differentiation, but maybe if you could frame the opportunity vis-à-vis potential entry of the orexin-based products. I think this has probably been asked in the past, but just wanted to see how you were thinking of the potential impact on the orexins, again fully knowing it is a polypharmacy market, but just trying to size the market opportunity here. Thanks.

Yes. As we shared before, this is a difficult-to-treat patient population. There is a lot of trial and error, and I think although there is a lot of enthusiasm for the orexin agonists, I think there is also recognition that not every patient is going to respond or necessarily get the same level of symptom relief across the spectrum of symptoms. So from our perspective, AXS-12, you know, has very strong data within cataplexy. There is daytime dosing, which is very appealing to patients, and the potential impact across functional scores as well. It is something that we hear in feedback is very promising. I think in terms of how the orexins will stack up relative to other treatments, including AXS-12, remains to be seen. But our expectation based on feedback from KOLs is that they expect polypharmacy to continue to exist significantly with the advent of a new mechanism of action in the space. Yeah. And if I may add, just as a reminder, in terms of mechanistically how these agents work, as we know, narcolepsy is a disease where we do have a loss of orexin neurons, and those directly stimulate the locus coeruleus which produces norepinephrine. So we target with AXS-12 norepinephrine. So it totally makes sense in a way both groups of products are targeting exactly the same pathway. That is one of the reasons why we are very excited about AXS-12. It makes sense mechanistically, and clinically, you know, what we have seen is not only very profound effects on cataplexy, but also positive effects on excessive daytime sleepiness and also on cognition, which we have measured pretty extensively in the program. In clinical studies that we have done, also based on the results from the long-term safety studies, these effects are consistent. The other thing that we like about AXS-12 from a mechanistic perspective is the fact that a majority of patients with narcolepsy do suffer from depression, and the mechanism of action of AXS-12 does kind of dovetail into that. So in a situation, in a clinical situation where you do have a lot of comorbidities, it is helpful to have a drug with a mechanism of action which could potentially maybe impact the other diseases which are neighbors of the primary condition. So really excited about AXS-12 and especially the fact that all these benefits are delivered with a very favorable safety and tolerability profile.

Thank you. We have reached the end of our question-and-answer session. I would like to turn the floor back over for any further or closing comments.

We thank you, everyone, for joining us on this call. Axsome is in a unique position to continue to deliver innovative medicines at the frontier of neuroscience to patients and providers. And through disciplined investment and performance across our commercial and development CNS portfolios, we expect to continue to generate significant value through the next decade and beyond, not only for patients, but for stakeholders. We look forward to keeping you all updated on these important milestones ahead.