Axsome Therapeutics - Q4 2025

Transcript

Operator (participant)

Good morning, and welcome to the Axsome Therapeutics fourth quarter and full year 2025 earnings conference call. My name is Kevin, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, there'll 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 it over to Ashley Dong, Director of Investor Relations. Ashley, please go ahead.

Ashley Dong (Director of Investor Relations)

Thank you. Good morning, and thank you all for joining Axsome'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, who 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 regulatory activities. These statements are based on current expectations and assumptions and are subject to risks and uncertainties that may cause actual results to defer 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, and the company disclaims any obligation to update such statements. With that, I'll hand it over to Herriot.

Herriot Tabuteau (CEO)

Thank you, Ashley. Good morning, everyone. 2025 was a year of significant commercial R&D progress at Axsome. Our commercial business is strong, with Auvelity achieving sales of over $500 million in its third full year of launch, Sunosi growth accelerating and Symbravo launching, adding a third pillar of growth. Total revenue for the fourth quarter increased 65% year-over-year to $196 million, and for the full year increased 66% to $639 million. Our innovative medicines continue to meaningfully improve patient outcomes. Just our current commercialized products have the potential to achieve multi-billion 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 a PDUFA action date of April 30th. If approved, Auvelity has the potential to address this prevalent and debilitating condition for which currently only one product is approved. As we approach the April 30th 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 II /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've 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. 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 engaged phase III trial of solriamfetol in this indication is progressing. 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 AZD7325, a novel oral GABA A alpha-2/3 receptor positive allosteric modulator. We plan to evaluate AXS-17, the new designation for this compound, for the treatment of epilepsy based on compelling data in preclinical seizure models.

... Further, AXS-17 has demonstrated a favorable safety profile in over 700 patients to date. phase II trial-enabling activities are underway. We look forward to provide updates on this new development program in the coming months. Taken together, our growing commercial business, the potential label expansion for Auvelity, and the robust innovation across our pipeline, uniquely position us to continue to deliver new treatment options for patients living with CNS disorders. With that, I'll hand the call over to Nick to review our financial results for the quarter.

Nick Pizzie (CFO)

Thank you, Herriot. 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 million for the fourth quarter and $638.5 million 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 Symbravo. Auvelity achieved net product sales of $155.1 million for the fourth quarter, up 68% versus the prior year.

Auvelity sales surpassed the $500 million mark in only its third full year from launch, totaling $507.1 million, representing a 74% year-over-year increase. Sunosi posted another strong quarter with net product revenue of $36.7 million, a 40% increase compared to the fourth quarter of 2024. Sunosi revenue was $124.8 million for the full year of 2025, representing a 32% increase versus last year. Symbravo generated $4.1 million in net sales for the fourth quarter and $6.6 million 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 and net discounts in the fourth quarter of 2025 were in the high 40% range. Going forward, we expect Auvelity and Sunosi gross net discounts to increase to the mid-50% range due to typical Q1 dynamics. Symbravo gross 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 $12.3 million and $47.5 million for the fourth quarter and full year of 2025, compared to $10.5 million and $33.3 million for the comparable periods in 2024. Research and development expenses were $48.8 million for the fourth quarter and $183.3 million for the full year of 2025.

That's compared to $55 million and $187.1 million 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 $169.3 million for the fourth quarter and $570.6 million for the full year of 2025. That's compared to $113.3 million and $411.4 million 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 salesforce expansion and the national launch of a direct-to-consumer advertising campaign, along with the commercial launch of Symbravo. Net loss for the fourth quarter was $28.6 million, or $0.56 per share, compared to a net loss of $74.9 million, or $1.54 per share for the fourth quarter of 2024. The $28.6 million net loss in the quarter includes $22.7 million in stock-based compensation expense.

Net loss for the full year of 2025 was $183.2 million, or $3.68 per share, compared to a net loss of $287.2 million, or $5.99 per share for the full year of 2024. This year's loss of $183.2 million includes $93.8 million of stock-based compensation expense. Now, turning to the balance sheet, we ended the year with $323 million in cash and cash equivalents, compared to $315 million 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'd like to now turn the call over to Ari, who will provide a commercial update.

Ari Maizel (Chief Commercial Officer)

Thank you, Nick. Axsome delivered strong performance in Q4 and completed 2025 with momentum for Auvelity, Symbravo, 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 remains 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 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 Symbravo, 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 Symbravo among the highest volume migraine prescribers in the U.S., and we are pleased with the feedback from HCPs on the positive impact Symbravo is having on patients.

The key clinical attributes leading to Symbravo 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 Symbravo's long-term potential as a preferred acute migraine treatment. We continue to make progress with Symbravo 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 Symbravo in Q4, which now enables negotiation with all major commercial payers and PBMs. We anticipate coverage for Symbravo to expand and evolve throughout 2026.

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 anti-obesity drugs 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 15,600 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 underscores the effectiveness of our commercial strategy and execution and positions us well as we enter 2026. Abilify, Sunosi and Symbravo 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.

Ashley Dong (Director of Investor Relations)

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

Operator (participant)

Certainly. We'll now be conducting a question and answer session. If you'd like to be placed into question queue, please press star one on your telephone keypad. We ask you, please ask one question, then return to the queue in order to conserve time. Our first question today is coming from Leonid Timashev from RBC Capital Markets. Your line is now live.

Leonid Timashev (Biotechnology Analyst)

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're running. I guess I'm curious, you know, whether you think that means that, you know, some of the studies in binge eating and shift work disorder could potentially be approvable on a single phase III. Similarly, why, given that policy, for example, you're running two studies in ADHD, splitting pediatric and adolescent patients? Thanks.

Mark Jacobson (COO)

Hey, Leo, this is Mark. Good morning. Obviously, that's hot off the press, and the team is assessing it. One thing, as always, we always vet our clinical plans with the FDA and the divisions that the programs are under. We're gonna continue to do that. You know, if there are changes, we'll see. You mentioned shift work disorder. That's an example where we already have alignment with FDA that the existing clinical package could serve as potential supportive evidence, should the study that we're conducting now be positive. That's one example where that's a place. I'll pass it to Herriot for, you know, thoughts on ADHD, but that, our plans for ADHD, that reflects, you know, recent alignment that we reached with FDA.

Herriot Tabuteau (CEO)

Yeah. Yeah. Just to add to what Mark was saying, one thing to keep in mind is, is although this is a broad guidance, each clinical situation, each indication is specific and, and has to be looked at from that perspective. For ADHD, this is a disorder which affects different patient populations. For example, adults with ADHD are different from children with ADHD. 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're conducting two studies in pediatric patients with ADHD because again, there is a sub-segmentation of pediatric patients. You have children, so those are individuals who are less than 12 years of age, and then adolescents.

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. That'll have no impact whatsoever on our eventual filing timeline.

Operator (participant)

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

Marc Goodman (Senior Research Analyst)

Yes, can you talk about AXS-17, just the types of epilepsy, the development plan that you're thinking about moving into? 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.

Herriot Tabuteau (CEO)

Thanks for the question. The product has been studied in different indications. One indication that it's been studied in, in the past is the generalized anxiety disorder, and all of the safety data and safety experience comes from those studies. It's 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, in, in 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. Right now, what we're doing is we have started the work to make sure that we are phase II ready.

Also, we are very closely assessing all of the various different epilepsies, in which the product and preclinical models has shown promise. Stay tuned, and over the balance of the year, we'll provide more details on which indication, exactly which specific epilepsy we will target first.

Operator (participant)

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

Jason Gerberry (Managing Director and Equity Research Analyst of Pharma and Biotech)

Hey, guys. Thanks for taking my question. Wanted to just follow up on the comment just about Auvelity payer coverage evolving over the course of the year. 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? The reason I ask, 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. Wondering how that looks for you guys with Auvelity and the ADA indication. Thanks.

Ari Maizel (Chief Commercial Officer)

Yeah, thanks for the question, Jason. As you stated, in general, when you have a product that's on the market for a specific indication, then you expand the indication, generally speaking, your existing coverage should apply to the new indication. I think what's unique about MDD and ADA is that MDD is largely a commercial business, whereas ADA is largely a Medicare business. Although we've had really good coverage across both commercial and Medicare, we have been spending more time with the Medicare Part D plans to ensure coverage and utilization management is sufficient to support ADA uptake.

The other part of the comment about evolving over the course of the year is, you know, we haven't hit 100% access for the brand, and that is something that is our aspiration. Just continuing to work with plans that don't currently cover the product, and continue to work on things like removing steps and PAs where, where, where they exist today.

Operator (participant)

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

Andrew Tsai (Managing Director)

Hey, good morning. Thanks for the update. 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? Maybe as an follow-up to the gross net specifically, where do you think combined gross to net for Auvelity could trend or shake out over time? Thank you.

Ari Maizel (Chief Commercial Officer)

Thanks for the question. You know, we don't generally guide on where we expect the ultimate uptake to land, but suffice to say, we're actively preparing for the launch to enable commercial availability, and customer engagement, you know, as soon as feasible, you know, post-launch. You know, from our perspective, there's very limited analogs in the market. Obviously, there's only one other product, so we're 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, share additional details about our commercial effort. Stay tuned for some more details later in the year.

Nick Pizzie (CFO)

Yeah. Hey, Andrew, it's Nick. Just maybe a note on the GTN. We anticipate that 70%+ scripts for ADA will be written in the Medicare Part D channel. As such, that channel has a more favorable GTN, specifically as there's no copay card utilization around that. We would expect potential favorability from where we've been on the aggregate for Auvelity.

Operator (participant)

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

Pete Stavropoulos (Director of Biotech Equity Research)

Good morning and thanks for taking my questions. For Sunosi, you know, you had double digit year-over-year growth. You know, 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? And are you seeing any differences in prescriber behavior between those two segments? Thanks

Ari Maizel (Chief Commercial Officer)

Yeah, thanks for the question, Pete. Yeah, Sunosi continues to deliver steady growth in both the OSA and narcolepsy markets. You know, as we shared before, approximately 70% of prescriptions are for EDS and OSA, and 30% for EDS and, and narcolepsy. I think over the course of the year, we saw a positive growth in new patient starts, total active writers and total prescriptions. Part of our strategy over the past two years has been driving depth across existing Sunosi writers. We're seeing growth from both, both ends, both OSA and narcolepsy, and really across specialty or prescriber segments, you know, including PCPs, pulmonologists, sleep specialists, and neurologists.

Operator (participant)

Thank you. Next question is coming from Benjamin Burnett from Wells Fargo. Your line is now live.

Speaker 23

Hey, guys. This is Craig on for Ben. I, 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? You, you all mentioned that Auvelity scripts continue to grow. However, the MDD market's been overall flat. Where is that growth coming from? Are you seeing adoption in earlier lines of care? Thank you. Bye.

Ari Maizel (Chief Commercial Officer)

Yeah, thank you for the question. Yeah, as, as you know, we launched a national TV campaign late in the year, around September, October timeframe. We've been pleased with the impact of that campaign. It, it did generate inflection in new patient starts. Our analysis of the impact by media channel has enabled us to optimize our spend going into 2026. Yeah, we'll have more details to share on, on that impact, you know, as we get through the year. In terms of where the growth is coming from, you know, we're pleased with efforts to expand use in primary care, while also driving continued growth in psychiatry practices. We are seeing really nice growth across all segments.

Primary care was the fastest growing segment in Q4, in terms of new patient starts and new writers. We expect that to continue to, to be a trend, as we expand our efforts in, in the primary care setting.

Operator (participant)

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

Ram Selvaraju (Managing Director and Senior Healthcare Analyst)

Thanks so much for taking my question. I was wondering if you could comment on what you expect ultimate reimbursement and 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? If so, you know, what do you expect the ultimate optimal range to look like? Thank you.

Ari Maizel (Chief Commercial Officer)

Yeah, thanks for the question. You know, our, our goal is, is to try to secure access for as many patients as possible across channels. Although we don't typically guide on what the, the final steady state covered lives percentage would be, I think you've seen for the past few years that we've made steady progress in terms of increasing covered lives. Our expectation is, is we'll continue to work to, to ensure access for both the MDD and ADA indication.

Operator (participant)

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

David Amsellem (Managing Director and Senior Research Analyst of Biotechnology)

Thanks. Coming back to AXS-17, sorry if I missed any commentary here, but can you talk about how you're thinking about it beyond epilepsy? For instance, it's been about 20 years since something's been approved for generalized anxiety disorder, given the mechanism, it would seem that could be an interesting avenue to explore. How are you thinking about broader development of the asset? 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.

Nick Pizzie (CFO)

You know, 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. As you know, you know, we recently 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 focused with the initial indication. We think that there's a lot of promise there, in that area, based on all of the preclinical work that's been done by others and also by, by our team.

Mark Jacobson (COO)

Stay tuned. You know, stay tuned, and I think it's a little premature to talk about add-on indications to the primary indication.

Operator (participant)

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

Ashwani Verma (Biopharma Equity Research Analyst)

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

Ari Maizel (Chief Commercial Officer)

Yeah, thanks for the question, Ash. The sales force expansion is designed to accelerate growth in MDD while providing scale for a potential indication approval in Alzheimer's agitation later this year. When you think about, you know, the expansion, you know, the national hiring reps throughout the country to increase reach and frequency to the highest value ACPs across specialties will enable us to capitalize on the momentum that we've created in the primary care segment. Primary care is of growing importance because of they are frontline treaters for both MDD and ADA. Then finally, it will allow us to engage with an expanded target universe. Larger sales force allows us to engage with a larger group of ACP targets.

When you think about the specialties that will be important for, for both indications, primary care, psychiatry, neurology, are really the largest specialty segments that we'll be focused on.

Mark Jacobson (COO)

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

Operator (participant)

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

Ami Fadia (Managing Director and Senior Biotech Equity Research Analyst)

Hi, good morning. Thanks for taking my question. My question is on Symbravo. 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? How should we see that impacting the growth to net or the rate of full through of prescriptions as the year progresses? Thank you.

Ari Maizel (Chief Commercial Officer)

Yeah, thank you, Ami. As we mentioned in the call, we secured a contract with the third large GPO, and as you'll recall, the GPO contract is really the precursor for negotiating with payers and PBMs to secure coverage. Although it doesn't guarantee coverage with the payers PBMs, it does allow for active negotiation. Our team is engaged with all the national payers and PBMs. You know, I think we're optimistic about the potential to increase Symbravo coverage. That is something that we're focused on primarily for this year, and we'll share some additional updates as we, as we secure access.

Mark Jacobson (COO)

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

Operator (participant)

Thank you. Our next question is coming from Joseph Thome from TD Cowen. Your line is now live.

Joseph Thome (Managing Director and Senior Biotechnology Equity Research Analyst)

Hi there. Good morning. Thank you for taking my question. Maybe just in terms of the potential Alzheimer's disease agitation launch, when will you be in a position to be able to launch the therapy after the April 30th date? Will it take some time before we could see, you know, kind of the, the full-fledged launch there? 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 disease agitation, or how can we best monitor how that specific launch is going? Thank you.

Ari Maizel (Chief Commercial Officer)

Thanks, Joseph. Yeah, we'll be ready to go within a quarter on ADA, obviously the team right now is preparing every aspect for launch readiness. So we're, we're feeling really optimistic about the, the potential impact, if approved. Then in terms of metrics, you know, we, we expect to share approximate percentage of scripts coming from the ADA space as we learn more. As you know, in the, the typical IQVIA or Symphony data, it's not breakout by indication. So we haven't finalized our plans, but we'll certainly be able to share some details about how the launch is going.

Operator (participant)

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

Sean Laaman (Executive Director)

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

Ari Maizel (Chief Commercial Officer)

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. You know, I think what's very clear is that not every patient responds to every mechanism in the same way, and there's a lot of trial and error. From our perspective, AXS-12 offers a very compelling treatment option for patients, both in terms of cataplexy relief as well as safety tolerability profile. We feel very optimistic. You know, it's a novel mechanism relative to what's in the marketplace today.

Based on the feedback we've received in market research, there is a high degree of interest in, in using this for, narcolepsy patients.

Operator (participant)

Thank you. Next question is coming from Myles Minter from William Blair. Your line is now live.

Myles Minter (Healthcare Research Analyst)

Hey, guys, congrats on the year. Just on AXS-17, just wondering how you're thinking about the therapeutic window there. In epilepsy, I know that being alpha-1 sparing should be less sedative than a benzo. I think in the hands of AstraZeneca in their phase II, they did show a little bit of sedation in that generalized anxiety disorder. Just wondering whether you're gonna play around with dose to try and dial that out, or whether the change in indication here is enough to make that an acceptable therapeutic window. Thanks, guys.

Herriot Tabuteau (CEO)

Yeah, we, we are-- Thanks for the question. We are exploring dose, and part of that exploration involves a lot of PK/PD modeling. We think that, based on the preclinical data as well as the clinical data, there's a range of potential doses. As, 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, that we, 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, some work there to be done and some information to be gotten from the initial trial in, in those patients. Stay tuned.

This is what research is about, but we're very excited about, the mechanism of action and the specificity of, the receptor targeting.

Operator (participant)

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

Matthew Harrison (Equity Research Associate)

Hey, guys, congrats on all the progress, and thanks for taking our question. We were thinking about the safety data for Auvelity and 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. 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.

Herriot Tabuteau (CEO)

Hey, Matt. Good morning. You know, thanks for the question. You know, the review is underway. By the way, just a reminder, since this is a priority review, we're, we're more than halfway through, and we're, we're just about two months out from PDUFA. It's a little early for us to comment on potential, you know, potential label. However, what we can share is we, we, you know, should the product be approved, we'd expect the safety profile to be described in the label in that patient population, and we'd be pleased with that. You know, I think that's as probably as much as we can say there. Could you remind me of the second part of your question, please?

Maybe, Ari, you want to field that?

Ari Maizel (Chief Commercial Officer)

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

Operator (participant)

Thank you. Next question today is coming from Joon Lee from Truist Securities. Your line is now live.

Joon Lee (Managing Director and Senior Biotech Analyst)

Congrats on the quarter, and thanks for taking the questions. This is awesome one for Joon. Just a couple from us. Are you eligible for priority review for the AXS-12 NDA submission? Just want to make sure I understand correctly, Nick, you're saying that the gross unit of Auvelity should actually improve after approval, given the Medicare population. Thank you.

Ari Maizel (Chief Commercial Officer)

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

Nick Pizzie (CFO)

Yeah, sure. Yeah, and, and correct, based on, yeah, assuming that we, would see that 70% plus in the Medicare Part D channel for ADA scripts, if that's how it evolves, we would anticipate that the GTN would be more favorable, as we're seeing currently in the Medicare Part D channel. That's, more favorable than the commercial channel.

Operator (participant)

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

David Hong (Senior Portfolio Manager)

Hi, thanks for taking my questions. Just on the breakdown between the community and long-term care settings for ADA, how that breaks down and how you're planning to deploy your sales force to address those two segments? If Bristol Myers Squibb's Cobenfy should be approved for the adjacent indication of ADP, do you think that could become a competitor in ADA, you know, such that if patients are being treated for ADP, that might also address their agitation? Thanks a lot.

Ari Maizel (Chief Commercial Officer)

Yeah, thanks for the question, David. As a reminder, about 60% of Alzheimer's disease agitation prescriptions are in community-based settings and, and 40% are in long-term care facilities. It remains to be seen how the uptake of AXS-05 will be across those settings of care, but that, that is sort of how the, the market is, is behaving at the moment. In terms of your question on Cobenfy, we, we do view Alzheimer's agitation and Alzheimer's psychosis as separate and distinct indications. We, we don't expect there to be much confusion in the marketplace, and agitation symptoms are, are the most prominent and most burdensome for patients. There's significant opportunity, significant unmet treatment needs, and, and that's, that will be our focus, you know, at launch, if approved.

Operator (participant)

Thank you. Next question is coming from Yatin Suneja from Guggenheim. Your line is now live.

Speaker 22

Hey, good morning, this is Eddie on for Yatin. Thanks for taking my questions. How should we think about the gross to net dynamics for ADA and how they're different from MDD? Then when, when looking at Auvelity penetration within the PCP market segment, can you talk about how big you expect that penetration to be versus the sort of more defined neuropsych segment? Thank you.

Ari Maizel (Chief Commercial Officer)

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

Herriot Tabuteau (CEO)

Eddie, I'm sorry, could you repeat your second, the second part of your question?

Speaker 22

Yeah, I was just wondering if you could talk about the overall penetration within the PCP segment versus the, like, more neuropsych focused segment in MDD for Auvelity.

Ari Maizel (Chief Commercial Officer)

Yeah, it's, you know, it's 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 haven't specifically shared where we expect the final penetration to land in MDD. 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've expanded our sales team and continue to penetrate the primary care segment. Where it will sort of end up at the end, is difficult to say at the moment.

Operator (participant)

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

Graig Suvannavejh (Managing Director)

Hey, good morning. Thanks for taking my question and 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-a-vis the 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's a polypharmacy market, but just trying to size the market opportunity here. Thanks.

Ari Maizel (Chief Commercial Officer)

Yeah. you know, as we shared before, this is a difficult to treat patient population. There's a lot of trial and error, and I think although there's a lot of enthusiasm for the orexin agonist, I think there's also a recognition that not every patient is going to respond, or necessarily get the same level of symptom relief across the spectrum of narcolepsy symptoms. From our perspective, AXS-12, you know, has very strong data within cataplexy. you know, there's daytime dosing, which is very appealing to patients. you know, the potential impact across functional functional scores as well is something that we hear in feedback is very promising. I think in terms of how the orexins will stack up relative to other, other treatments, including AXS-12, remains to be seen.

Our expectation based on feedback from KOLs is that they expect polypharmacy to continue to exist significantly, even with the advent of, of new mechanisms of action in the space.

Herriot Tabuteau (CEO)

Yeah. If I may, if I might add, too, just as a reminder, in terms of mechanistically, how these, these agents work, as we know, narcolepsy is, is a disease where we do have a loss of orexin neurons, and those directly stimulate the locus coeruleus, which produces norepinephrine. We target with AXS-12, norepinephrine. It totally makes sense. In, in a, in a way, both groups of products are targeting exactly the same pathway. That's one of the reasons why we're very excited about AXS-12. It makes sense, mechanistically and clinically. You know, what we've seen is not only very profound effects on cataplexy, but also positive effects on excessive daytime sleepiness and also on cognition, which we've measured pretty extensively in the program.

In the clinical studies that we've done, and 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. The mechanism of action of AXS-12 does kind of dovetail into that. 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.

We're really excited about the AXS-12 and especially the fact that all these benefits are delivered with a very favorable safety and tolerability profile.

Operator (participant)

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

Herriot Tabuteau (CEO)

Well, 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. 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.

Operator (participant)

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.