Axsome Therapeutics, Inc. Price & Performance (AXSM)

Thank you. Good morning and thank you all for joining us on today's conference call. This morning, we issued our earnings press release providing a business update and details of the company's financial results for the fourth quarter and full year of 2024. The release crossed the wire a short time ago and is available on the Investors section of our website along with the earnings presentation accompanying today's call. Those joining via webcast may advance through the slides at any time during the discussion. During today's call, we will be making certain forward looking statements regarding, among other things, the efficacy, safety and intended utilization of our investigational agents, our clinical and non clinical plans, are planned to present or report additional data the anticipated conduct and the source of future clinical trials, regulatory plans, commercial plans, and possible intended use of cash and investments. These forward looking statements are based on current information, assumptions and expectations of future events that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission including our quarterly and annual reports.

You are cautioned not to rely on these forward looking statements which are made only as of today's date, and the company disclaims any obligations to update such statements. Joining me on the call today are Doctor. Ario Tabito, Chief Executive Officer Nick Pizzi, Chief Financial Officer Ari Maisel Chief Commercial Officer Hunter Murdock, General Counsel, and Mark Jacobson, Chief Operating Officer. Aerio will begin with opening remarks in including an overview of the important progress we've made in 2024 and the look ahead into the rest of 2025. Following Aria, Nick will review our financial results and then Ari will provide a commercial update. We will then open the line for questions, which will be taken in the order they are And with that, I'll turn the call over to Aria. Thank you, Darren, and good morning, everyone.

In the last two point five years as a fully integrated R and D and commercial organization, Axsome has both expanded and deepened its leadership within CNS.

Portfolio today comprises three differentiated in market products three innovative product candidates in regulatory submission stage, and numerous ongoing Phase three trials.

This broad portfolio positions us to potentially commercialize seven products or indications through 2027, allowing us to deliver significant innovation to patients, and value to shareholders. 2024 was another year of strong execution for For the year, we delivered total net product revenue of 300 East million dollars reflecting high double digit year over year growth for Velvety and Sonozi. We expect continued growth in 2025 supported by our second completed sales force expansion for VELITY, further improvements in market access dynamics and increasing awareness of our differentiated products. Based on the recent performance, Ovelity is on track to reach blockbuster potential Most recently, we received U. S. Approval of SYNBRAVO on January 30, representing a novel oral acute treatment for migraine.

Based on its clinical profile, SYMBROVO represents an important development for patients living with migraine.

With SYMBARRVO, we now have three commercial stage products and are actively preparing for its commercial [indiscernible] Before turning the call over to Nick and Ari, who will expand on the strong financial and commercial performance in the year, I'd like to provide an update on our rapidly advancing late stage pipeline and speak about key priorities for 2025. 2024 was highly productive from a clinical development As we read out five pivotal trials initiated three Phase three trials across our portfolio. [indiscernible] Our R and D execution in 2024 positions us to potentially deliver several important milestones in 2025. Starting with PXS-five, the treatment of Alzheimer's disease agitation, Last year, we completed a Phase three clinical program this indication, which consisted of four controlled Phase III efficacy trials and a long term safety trial. With the positive results from this comprehensive program in hand, plan to submit an NDA for AXS-five for the treatment of Alzheimer's disease at the FDA in the second half of twenty twenty five. Moving on to AXS-twelve, for the treatment of norecolepsy with cataplexy. Last year, we also completed the clinical program for this product candidate which included three controlled efficacy trials and a long term safety trial Based on the positive results from these studies, we plan to submit an NDA for AXS-twelve the treatment of cataphlexy in patients with narcolepsy to the FDA in the second half of twenty twenty five.

As it relates to our NDA4 AXS-fourteen in fibromyalgia, are in publication stage of the submission and expect to submit the NDA to the FDA this quarter. Apart from the we anticipate top line readouts from several Phase three trials in the near term. These include the IMerge Phase three trial evaluating SYMBARROVO in patients with prior inadequate response to oral CGRP inhibitors the FOCUS Phase three trial of solriamfetol in ADHD, and the PARADYM Phase three trial of solriamfetol major depressive disorder. Top line results for all three of these studies are on track for the first quarter of twenty twenty five.

Enrollment for the ENGAGE study of solvary and vikold in binge eating disorder the sustained study of solvaryngretol in shift work disorder, continuing to progress. With top line results for both studies anticipated in 2026. All in all, across our development portfolio, we expect NDA submissions for three product candidates and top line readouts from three Phase three trials in the coming months. I am proud of the excellent progress we've made as an organization and look forward to another transformative year as we build upon our commercial success and advance our CNS pipeline. With that, I'll hand the call over to Nick. Thank you, Ariel.

Today, we'll discuss our fourth quarter and full year 2024 results.

And provide some financial guidance. Total product revenues were 118,800,000.0 and $385,700,000 representing year over year growth of 6688% respectively.

This consisted of net product sales of 100 and and $17,300,000 and $381,700,000 for the fourth quarter and full year of 2024, and royalty and milestone revenue of $1,400,000 and $4,000,000 respectively. Total product revenues for the comparable periods in 2023 were $71,500,000 and $204,900,000 Of LDT net product sales were $92,600,000 and hundred and $91,400,000 for the fourth quarter and full year of 2024, representing 89124% year over year growth.

Avelby net product sales for the comparable periods in 2023 were $49,000,000 and $130,100,000 Denosi net product revenues were were $26,200,000 and $94,300,000 for the fourth quarter and full year of 2024, representing 1626% year over year growth consisting of 24,700,000.0 and $90,300,000 in net product sales, and $1,400,000 and $4,000,000 in royalty and mile [indiscernible] Q4 includes a one time $500,000 regulatory based milestone earned by Axsome. Denosi net sales with comparable periods in 2023 were $21,700,000 and $72,400,000 Total Sanofi revenue for the full year of 2023 was $140,500,000 which includes license revenue of $65,700,000 from out licensing Sanofi in certain ex U. S. Territories.

Total cost of revenue were $10,500,000 and $33,300,000 for the fourth quarter and full year of 2024.

Total cost of revenue for the comparable periods in 2023 were $7,400,000 and $26,100,000 Q4 cost of revenue includes a one time $2,500,000 expense for the achievement of a sales based milestone related to worldwide Sanofi sales.

Total cost of revenue for the full year 2023 included a one time cost of $5,000,000 associated with the revenue received on out licensing Sanofi in certain ex U. S. Territories. Research and development expense were $55,000,000 and $187,100,000 for the fourth quarter and full year of 2024, respectively, compared to $30,800,000 and $97,900,000 for the comparable periods in 2023. The increase was primarily related to the company's ongoing Phase III trials of solvriamfetol in ADHD, [indiscernible] binge eating disorder and shift work disorder. The advancement of Phase three trials of AXS-five and AXS-twelve, manufacturing costs for AXS-seven and AXS-fourteen, as well as higher personnel costs including non cash stock based compensation, associated with organizational growth.

Selling, general and administrative expenses were $113,300,000 and $411,400,000 for the fourth quarter and full year of 2024, respectively.

Compared to $86,800,000 and $323,100,000 for the comparable periods '23.

The increase was primarily related to commercialization activities for Avelady and Sanofi, including sales force and marketing expenses, and higher personnel costs, including non cash stock based compensation Net loss for the fourth quarter of twenty twenty four was $74,900,000 or $1.54 per share compared to a net loss of $98,700,000 or $2.08 per share the comparable period in 2023. The net loss in the fourth quarter of twenty twenty four includes $35,900,000 in non cash charges comprised primarily of $22,000,000 in stock based compensation expense and $11,000,000 in acquisition related contingent consideration expense. Net loss was $287,200,000.0 or $5.99 per share for the full year of 2024 compared to a net loss of $239,200,000 or $5.27 per share for The net loss for the full year includes total non cash charges approximately $125,000,000 which includes $85,200,000 in stock based compensation expense $28,100,000 in acquisition related contingent consideration expense, and $6,400,000 in intangible amortization, compared to $62600000.048900000.0 dollars and $6,400,000 respectively for the full year of 2020 Avelty and Sanofi GTN discount in Q4 of twenty twenty four were both approximately 50%. Due to negative seasonality effects in Q1, we anticipate that GTN discount for Aveliti and Sanofi to be in the mid-50s.

We ended 2024 with $315,400,000 in cash and cash equivalents compared to $386,200,000 at 12/31/2023. We believe that our current cash balance is sufficient to fund an anticipated operations into cash flow positivity based on the current operating plan. Would now like to turn the call over to Ari, who will provide a commercial update. Thank you, Nick. Axsome delivered another strong quarter of demand growth for Avelity and Sanofi in the fourth quarter of twenty twenty four. Capping off a successful year of increased awareness and utilization of our medicines. For both products, patients and providers continue to report a significant positive impact on both symptoms and quality of life measures.

Our performance throughout 2024 is a testament to the impact of dynamic digital centric commercialization platform which has enabled consistent growth across our portfolio and is poised to support the launch of SYNBRAVO as an acute migraine treatment for adults in Avelity once again led the market in total demand growth for the quarter. With approximately 158,000 prescriptions representing 10% quarter over quarter growth and 87% growth compared to fourth quarter of twenty twenty three. By comparison, the antidepressant market less than 1% sequentially and grew 2% compared to the fourth quarter of twenty twenty three. Nearly 26,000 new patients were prescribed ALVETY in the quarter bringing the total number of new patients started on Aveliti since launch to approximately one hundred and sixty five thousand. Our sales team successfully activated 4,100 new providers in Q4.

Primary care providers representing the greatest source of prescriber growth. Avelady experienced meaningful positive with increases in total covered claims. Avelity access is seventy eight percent of all lives across channels. And sixty three percent of lives in commercial. Importantly, our market access team is actively engaged with payers across the payer landscape to expand and improve access in 2025. Moving on to Sanofi, total prescriptions were approximately 49,000 representing 4% sequential growth and 16% growth versus Q4 twenty twenty three.

By comparison, the waste promoting agent market grew 1% and grew 5% compared to the fourth quarter of twenty twenty three.

Approximately 4,100 new patients started Sanofi in the quarter, bringing the total number of new patients started on Sanofi to approximately 81,000 since launch.

Approximately 400 new writers were activated in Q4, resulting in a total cumulative prescriber base of nearly four Payer coverage for Sanofi in Q4 was stable. With eighty three percent of lives covered across channels.

Finally, we are excited to launch our third product SimBravo in the coming months. SYMBRAVO represents an innovative and highly differentiated treatment for migraine. Migraine remains the leading cause of disability among neuro and more than eighty percent of migraine patients discontinue their acute migraine treatment in the first year of treatment. Feedback from headache specialists and neurologists clearly existing treatments. We look forward to sharing additional details of our commercial launch plan soon. In closing, 2024 was a very successful year for Axsome. Our second full year as a commercial enterprise and we are very pleased with the growth of both Avelity and Sanofi. Our robust commercial capabilities and innovative digital centric commercialization platform position Axiom to deliver on the promise of our pipeline and improve the lives of those impacted by CNS conditions. I will now turn the call back to Darren for Q and A. Thanks, Ari. Operator, may we please open the line for questions. And the first question today comes from the line of Ram Selvaraju with H. C. Wainwright.

Thanks so much for taking my question. With respect to DTC promotional activities, whether those are for Orvelity or SimBravo, Can you comment on the cadence with which you expect those to be initiated? And what strategies you might employ in order to optimize the efficiency of DTC buys? Sure. Yes. Thanks for the question, Ram.

As we've discussed previously, we intend to launch a broad based media outreach plan for Avelity. This year in the coming months. And the way we think about it is ensuring that our spend is sufficient to drive awareness amongst patients and remain competitive in the depression market where most of the branded agents are advertising pretty broadly. In terms of sort of the media plan, we haven't commented on that specifically. But there are some calendar year seasonality consideration that we'll take into account and just make sure that when we are investing in media that it's during a time of the of the year that makes sense where patient flow and HCP offices is at a high level? Regarding Sun Bravo, we haven't commented on commercial go to market plans yet, but expect to share some more details in the coming months.

Thank you. Our next question is from the line of Charles Duncan with Cantor Fitzgerald. Please proceed with your question.

Yes, good morning, Ariel and team. Thanks for taking the question and congratulations on a nice year. For commercialization as well as the products for pipeline productivity I had a question with regard to the sales force expansion for [indiscernible] if you could provide any color on the relative size or change. And then whether or not that is going to create synergies with the prescriber base, the future prescriber base for Subrava and how that might happen? Sure. Yes. Thanks, Charles.

So as we mentioned previously, we added approximately 40 additional representatives to the OPELVITY sales team. That's about 10% to 15% increase in sort of the overall overall sales force size.

And yes, I think your question about synergy with ZimbraVO particularly when you think about migraine treaters in the primary care setting, we do believe that there's some overlap that we'll be able to take advantage of And so more to come on that, but one of the key aspects of our Port the high overlapping comorbidities with depression. Across all of the indications that we're studying. And so there does create some synergy or efficiencies with certain providers.

That makes sense. If I may just ask a quick pipeline question, that's on AXS-five. You've mentioned second half of the year for submitting the NDA.

I believe that that's gated by a stability test. So analysis ongoing. So I'm wondering if you have any greater color, would you anticipate that in third quarter or fourth quarter? I know you're really busy with a lot of NDA submissions now.

Hey Charles, it's Mark. Good morning. Thanks for the question. So just to clarify one thing. The rail link step is is building the submission. It's not a stability time point. That's the the gating factor.

And second half, you can expect updates for us from us, but it is a top priority. For the organization. And so we'll be looking to do that as early in the second half as possible, but we'll provide granularity as we get closer.

Thanks Mark. Thanks for taking the question. Thanks Charles.

The next question is from the line of June Lee with Truist Securities.

This is Asum Rana on for June. Congrats on the quarter and thanks for taking the questions.

Will the Alzheimer's disease agitation filing be an NDA or an SNDA?

And then, I had the pre NDA meeting for AXS-twelve for Nircolip and what are some of the wiggling scenarios?

I'll take the first one, this is Mark again. So we haven't communicated the filing approach just yet.

But you can expect to hear that from us in the not too distant future.

And I'm sorry, can you could you repeat the second question on 12?

Yes, sure. Just have you had the pre NDA meeting for AXS-twelve from narcolepsy? And just some labeling scenarios that you might see?

We haven't yet confirmed the timing around the meeting. But I think as soon as we have outputs, we'll look to share that with you all. And scenario planning, I think we're so close, so that's or commenting on different scenarios is the hypothetical that we're so close, I think we can [indiscernible] To share specifics with you on the strategy. Thank you.

Next question is from the line of Joseph Stone with TD Congrats on the progress and thank you for taking my question. Maybe just given the upcoming data ADHD, what is sort of a clinically meaningful change on the AISRS that you're looking for? And is Supernus' Calbri a a good comp here in terms of, I guess, overall data package and sort of the progress of their launch. Anything different with some story on the top that you can point out that might be particularly differentiated would be helpful. Thanks Joe. We're very close to announcing results for the Phase three trial.

In ADHD. So a lot will depend upon what the results show. We're just as excited as the rest of you to open the envelope and learn about the clinical profile. In a multicenter study. As it relates to what we're looking for, with regards to the study, What we're looking for is this would be a positive trial that is that is a study which meets its primary endpoint. And we're not looking for any specific difference between the treatment arms. This is the first study that we are conducting with Solvionfo in ADHD. And as it relates to your question, comparing it to Calgary, that remains to be seen. So we'll have to look at the data and we'll know soon.

The next question from the line of David Hong with Deutsche Bank.

Hi there. Thanks for taking my question. Congrats on the successful quarter and fiscal year. I was wondering if you could just talk a little bit about the expectations for seasonal cadence of scripts and revenues for Avelodi in 2025.

Particularly Q1 where we typically see some headwinds. How the sales force expansion efforts might pull through and if you would feel comfortable providing forward looking guidance for the product at some point? Thanks.

Yes. Thanks, David, for the question. In terms of seasonality from a demand standpoint, we do expect Q1 to be a growth quarter, but something somewhat slower growth than what we experienced in the back half of the year. We are optimistic of the impact of of the sales force expansion. We've already seen very good leading indicators in terms of sales activity, call activity, And if you recall from last year when we had another expansion, we started to see the impact of that team towards the end of Q1 which initially showed up as incremental growth in weekly NBRx or new patient starts. So we would expect something similar I think historically when you look at the depression market Q1 and Q3 the summer months tend to be somewhat slower than others for the overall market, but Auvility is a growth brand. We expect to drive meaningful growth throughout the course of the year. But there will be some dynamics that the overall market will experience.

Yes. David, it's Nick. As it relates to providing sales guidance, with the fluid nature of many of the market dynamics and unpredictability of external factors, which include payer coverage, field force expansion and other promotional efforts that could have material impacts. We don't plan to provide sales guidance currently. What we have shared and you can reference the deck that's been filed is that for Aveliti peak sales for Aveliti in MDD alone are in the $1,000,000,000 to $3,000,000,000 range.

For Synosin, its current indications $300,000,000 to $500,000,000 And then also for SunBravo $500,000,000 to $1,000,000,000 in revenue. So we remain confident in these ranges and as we continue to commercial guidance.

Thank you. Next question is from the line of David Amsellem with Piper Sandler. Please proceed with your question.

Hey, thanks. So my one question is this. So with with the exclusivity runway for Aveliti, shored up and with good visibility to significant cash generation. How are you thinking about M and A slash BizDev in terms of your ability and willingness to bring in an asset or assets where you can leverage the commercial infrastructure that you have in place or alternatively would you even bring in a development stage asset? Just let us know how you're thinking about that philosophically. Thanks.

Sure.

Yes.

Hey, David, it's Nick again. We are always looking for opportunities. We're obviously very satisfied with where we are with our late stage pipeline and our commercial assets. But something that potentially can complement something earlier stage in our pipeline. We are open to. We have dedicated resources internally now to evaluate opportunities and that is something that's on our radar.

Thank you. The next question is from the line of Mark Goodman Leerink Partners, Please proceed with your question.

Nick, can you help us with how to think about expenses this year And secondly, just on AXS-twelve, second half, for filing, can you just give us what the gating factors are to wait for that filing? Thank you.

Yes, sure. Mark, it's Nick. So I'll speak a little bit about the OpEx. And the quarter as well as 2025. R and D spend was slightly higher during the quarter as we were closing out the three eighty eight trials. And continuing to progress on all the other programs We anticipate the R and D spend peaked this quarter, Q4.

And do expect R and D spend to moderate in 2025 given the conclusion of the ADA trials and other trials concluding in Q1. As it relates to OpEx, we do expect to see an increase versus Q4. However, we expect sales to increase at a fast rate, putting us on track to achieve cash flow positivity. We're starting to see leverage in the P and L and sales growing faster than OpEx, which we're super excited about. Good morning, Mark.

With respect to ASUS 12 and the NDA, So we did share, we plan to have a pre NDA meeting with the FDA. So that's a component. But the rest is just building the modules and building the submission itself. The clinical the clinical program is done. So, it's it's really a lot of back office work now.

In order to get to that filing date. And then the other consideration that I'll just mention is this is the same division as as AD Education. So you might expect that we'll be running some air traffic control in terms of how we're working to choreograph workflows and things like that.

Thanks.

Our next question is from the line of Greg Silvania with Mizuho Securities. Please proceed with your question.

Thanks so much.

Thanks for taking my questions. Congratulations on all the progress in the quarter and the past past year. Just two quick questions for me. One, just on the PARADYGM study for solariamfetol and MDD. Expectations there and could you just remind us of the positioning, if you were to see a positive readout in MDD, the positioning of that product, especially vis a vis Aveliti?

And then just on SYM BRAVOVID, can you provide a sense of what you think the launch trajectory and uptake might look like? I think risatriptan is like second most prescribed drug generically at least for migraine. And so would would the expectation be a relatively smooth uptake or do you think it could be more gradual given maybe some education around the product? Thanks so much.

Great. Thanks for the questions. I'll take the first one. As it relates to the paradigm study and expectations, this is PARADIGM will be the first study that we're conducting with solriamfetol in MDD. So we're very close to having a readout. So we'll learn a lot from that. As it relates to potential positioning, you know, solvamfetol is approved to treat excessive daytime sleepiness. And there is a lot of overlap in terms of comorbidities between excessive daytime sleepiness and depression.

So a natural fit or natural way to look at this product if it were to have effect in MDD would be to position it for patients who have those two comorbidities. So we've disclosed that one of the ways that we conducted the study is to also look at patients who have EDS and MDD versus those who have MDD without EDS. And so that will provide us some very nice information about how the product works [indiscernible] and how the mechanisms of action which we think are very relevant, would translate clinically to appropriate fiction Hey, Greg. This is Ari.

So regarding the Synbravo uptake, obviously, there there are we're very optimistic about the impact SYNBRAVO will have on the acute migraine market When you look at analogs, we believe the more recent launches are probably more accurate in terms of uptake. I'm The product does does have a unique clinical profile relative to both the triptans as well as the oral CGRPs. So we do think that there is a very compelling position for the product.

But that said, one of the things that You should think about when modeling sub Bravo is we are being very targeted, very focused headache specialists and neurology practices.

That make up roughly 70% of the overall branded market And so and we'll be launching with something smaller than the two large oral CGRP competitors out there. So it remains to be seen exactly what the uptake will look like, but I do think that those are probably the closest analogs to assess. So first going back to the ADA filing plan for the second half of the year, know you're not guiding to specifics on the filing strategy, but could you help us understand I guess some of the regulatory and commercial factors feeding into how you're thinking about NDA versus sNDA what the practical implications could be of one path versus the other. And then secondly, I think you released mentioned that the AXS-fourteen NDA submission is on track for 1Q twenty five for fibromyalgia. I was just wondering if you could talk a bit about patient segments [indiscernible] could be a good fit for fibromyalgia assuming it's approved and what you see as the commercial potential there? Thank you. I'll start with the question about the different considerations for the filing [indiscernible] It's cross functional, right? There can are considerate considerations with respect to intellectual property, market access strategy, and some regulatory considerations.

So it really touches on every element of development and launch And I think we'll be able to comment specifically in the not too distant future, which path we're taking. Yes. As it relates to fibromyalgia, [indiscernible] One of the aspects of the disease is that it has multiple symptoms.

And the current treatment options do not adequately address all of those symptoms.

So So what's nice about the profile of AXS-fourteen to date is that not only does it reduce pain, but it also reduces it improves function and it reduces multiple symptoms of fibromyalgia. One key symptom of fibromyalgia that the data has shown could be really impactful to patients. And that AXS-fourteen does have an effect on its fatigue, which is which is very difficult to treat. And patients consider it to be one of the top three symptoms of fibromyalgia that results in their disability. So we're very excited about the potential for AXS-fourteen in fibromyalgia, especially given large patient population.

Got it. Thank you. For Jason.

We just had a couple on fulramphetol for ADHD. Just one follow-up regarding the Phase three clinical profile. Would your 1 to $1,500,000,000 in peak sales estimates change at all if we did see stimulant like efficacy the PARADIGM trial, which is maybe around that twenty percent to twenty five percent placebo adjusted benefit on AISRS endpoint. And then can you just remind us what your plans are for the adolescent population? And maybe how should be thinking about the size of the adult versus adolescent opportunity in terms of market share? Thanks.

Sure.

The ADC patient population is is so large and that still remains underserved despite the various treatments that are available. I don't think that will be very sizable market opportunity for SolRe and Fertal should the studies be positive. So we're very close to having a data readout, so we look forward to learning more about the efficacy profile of the drug potentially. In ADHD. As it relates to the pediatric population, a reminder, we we must generate data in the pediatric population in order to be able to submit an NDA to the FDA for consideration for ADHD. And so that is something that we plan to do. So we've talked about initiating that study and launching that study. In order to do that, we do need to get feedback from the FDA on the pediatric study plan. And that is in progress. Thank you. The next question is from the line of Lianud Timmieshev with RBC Capital Markets. Congrats on the progress.

I just wanted to ask on maybe some additional color on the patent settlement around Aveli with Teva. I guess first, how did you end up deciding on sort of the 02/1938, 02/1939 boundaries? And then maybe bigger picture, guess how does it change your peak assumptions for Avelity versus what you put forth in the slide deck around both MDD and Alzheimer's [indiscernible] [indiscernible] Thanks for the question. This is Hunter. I'll take the first part first and then Nick do you want to take that?

So the updates were just a negotiated resolution. It didn't tie you a specific [indiscernible] Nick, do you want to Yes. With the recent developments on the LOE we do plan to update and refine our guidance as the launch progresses and having the LOE day will help facilitate that process. So stay tuned. Our next question is from the line of Serena Chen with Wells Fargo. Please proceed with your question.

Hi, thanks for taking my question. I wanted to ask about SunBravo.

Just given the high rebating environment around oral CGRPs, how should we think about factors that could impact net price and anything differentiated Axsome is doing to compete there?

Yes. Thanks for the question. We'll obviously have a lot more to share as we prepare for the commercial launch. But as you mentioned, this is a high rebate category we also saw the Oral CGRPs launch with significant free goods in the market. And so we've been able to study the dynamics of those launches to formulate our our strategy and plan for engagement with payers. We feel very, very confident in the clinical profile of SYNBROVO. The fact that we have data across pain intensities very compelling data providing relief or pain freedom and freedom from both bodies bothersome symptoms at two hours, extended twenty four hours. There's a very strong clinical rationale for ZYNBRO. And in our early discussions with payers, we do see the potential to engage in access discussions for the brand. So we'll be able to share more as we get closer to the launch, but we are very mindful of building access while also maintaining long term profitability for the brand and that's one of our key areas of focus. The next question is from the line of Amy Sadia with Needham and Company. Please proceed with your question.

Thanks for taking my question. With several assets in late stage can you maybe just talk about your philosophy or how should we think about operating margin evolution over the next two, three years? And specifically just for this year as well with the launch of SunBravo, maybe if you can give us some more granular color on how to think about operating expenses that would be helpful. Thank you.

Sure. I'll handle I'll start with the second question first. Just as we successfully launched the Velvety, we're going to take a strategic approach in launching some bravo plan to continue to assess the investment over time.

First and bravo, we're confident in our ability to execute with an efficient SG and A spend in 2025 by leveraging our DCC approach and investors needed to build consistent growth trajectory, over the long term, The approval subsequent launch of Sembrada has always been factored into our cash runway. And as a reminder, current cash does take us into cash flow positivity.

As we think about operating margin over the next couple of years, We have the same strategies that that we've always had with ABILITY as well as Sanofi.

Very focused on ROI. And being mindful of how we invest in each dollar within the SG and A as well as in the R and D to ensure that we get the ROI top line. From the line of Ethan Suneja with Guggenheim Partners. Please proceed with your question. Hey, guys.

Thank you for taking my question.

Thanks for all the progress. Just a question on AXS. 12 or Ruboxetine. Curious to hear how you're thinking about the narcolepsy market in general. I mean, we have gotten mixed feedback from the from the QL specifically given that it is an SNRI. But you definitely have very interesting data that you have generated across multiple Phase III programs. So how should you how are you thinking about that program, the opportunity there? And any impact from Oraxane that could have on this sort of indication?

Yes. Thanks for the question. We're very optimistic about the impact of AXS-twelve and We recognize that there will be some education around the mechanism and the product and what makes it unique relative to some of the generic SNRIs that have been used historically But in terms of market opportunity, this is very compelling market approximately one hundred and eighty five thousand patients suffering from narcolepsy, seventy percent of those suffer from cataplexy. And dissatisfaction, inadequate response with existing treatments is very, very high. So we see a real opportunity for AXS-twelve in this marketplace and we'll share some more details on our thinking on the approach that we'll take as we get a little bit closer the filing.

The next question comes from line of Myles Winter with William Blair. Please proceed with your question. Hi. Thanks for taking the question. Maybe one for Nick.

Is there any material impact of the Medicare Part D restructure that took effect Jan one? On a Validi revenues. And I'm also wondering what the mix is of patients that are getting access to Avelady through the Medicare system versus commercial payment? And if that ratio is going to change over the next few years? Sure, Miles.

As released to Part D, we don't expect a significant impact. There might be just a little bit of a change in how GTN of overall, we don't anticipate an impact at this point.

Yes. And related to the mix, so currently, Avelodi is [indiscernible] We don't expect any significant changes to that. Obviously, with the potential for AXS-five and Alzheimer's agitation, there will be a much heavier focus on Medicare for that product. That indication. And so we'll have to share some more as we finalize our plans around NDIS NDA. Thank you. Our final question is from the line of Joel Beatty with Baird.

Please proceed with your question.

Good morning. This is Chris Chen on for for Joel. Just a question on Axsome. Not in ADA, but in smoking cessation. Just wondering if you could add a little more color on maybe a potential timeline in 2025? And then Just more specifically, are you incorporating The difference any differences between users of traditional cigarettes versus e cigarettes?

Thanks for the question. So we're Right now where we are in terms of the plans for the Phase three trial, we're very confident that we'll start this year. So we're looking forward to sharing with you more of the details. Of the study design, the initial trial will look at patients who smoke cigarettes. And in terms of your patients to use other forms of nicotine, that will come at a later date. But for our registration trial, it will be in the smokers.

Thank you.

At this time, there are no additional questions. I'll hand the floor back to management for closing remarks.

Thank you for taking the time to join today's call. 2024 was a busy year for the company the continued success across all aspects of our portfolio, As we sit here today, on February 18, our business reflects an expanding commercial enterprise rapidly advancing late stage neuroscience pipeline, poised to deliver potentially five innovative products in 10 serious neuropsychiatry conditions that collectively impact the lives of more than one hundred and fifty million people in The U. S. Alone.

Look forward to updating you on our continued progress throughout the year. Thank you. Have a great rest of your day.

This will conclude today's conference.

May disconnect your lines at this time. Thank you for your participation.