AXSM - NASDAQ

Greetings, and welcome to the Axsome Therapeutics First Quarter 2025 Conference Call and Webcast. At this time all participants are in a listen-only mode. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to your host, Darren Opland, Director of Corporate Communications at Axsome Therapeutics. Darren, please go ahead.

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 first quarter of 2025. 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’ll 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, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development 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 obligation to update such statements. Turning to today's agenda. Dr. Herriot Tabuteau, our CEO, will open today's discussion with an overview of our performance and key upcoming catalysts; Nick Pizzie, our Chief Financial Officer, will review our financial results for the quarter; Ari Maizel, our Chief Commercial Officer, will then provide a commercial update; Mark Jacobson, our Chief Operating Officer; and Hunter Murdock, our General Counsel, will be joining us for Q&A. And with that, I will turn the call over to Herriot.

Thank you, Darren and good morning, everyone. Axsome entered 2025 with strong momentum across the business. In the first quarter, we delivered year-over-year total revenue growth of 62%, driven by robust underlying demand for Auvelity and Sunosi. In addition, the recent FDA approval of Symbravo, our second internally developed product, reflects Axsome's commitment to delivering innovative medicines with the potential to meaningfully improve upon the standards of care for patients living with serious CNS conditions. Our portfolio today is distinctively diversified and strategically positioned to drive durable growth. Earlier this year, I outlined key priorities related to our pipeline. The first was to advance our 3 novel NDA stage product candidates toward regulatory filings. These include AXS-14 for the management of fibromyalgia, AXS-05 in Alzheimer's disease agitation and AXS-12 for the treatment of cataplexy and narcolepsy. The second was to successfully execute across our multiple Phase III clinical programs that broaden the potential of our current products and product candidates, including AXS-05, Solriamfetol and Symbravo. Since just the beginning of this year, we've made significant progress on both fronts, which underscores the agility and operational excellence of our organization. Starting with AXS-14 for the treatment of fibromyalgia. We have submitted our NDA to the FDA for AXS-14, and anticipate a decision on the acceptance of the filing in the second quarter. Fibromyalgia is a chronic and often debilitating the vision characterized by widespread pain, fatigue, sleep disturbance and cognitive impairment. Recent research suggests that there are over 17 million people in the U.S. who are living with fibromyalgia. Despite this prevalence, there has been no meaningful therapeutic innovation in more than 15 years while currently available treatment options offer variable efficacy and do not address all key symptoms of this condition. AXS-14 has the potential to address this unmet medical need in the treatment of fibromyalgia if approved. Turning now to AXS-05 for the treatment of Alzheimer's disease agitation. In March, we announced a positive FDA pre NDA-meeting minutes regarding our planned supplemental NDA submission for AXS-05 in the syndication, which reinforced our key assumptions related to our data package and filing timeline. We continue to make steady progress here and anticipate submitting the sNDA to the FDA in the third quarter of this year, with a potential FDA decision and launch in 2026 if approved. AXS-05 has been granted breakthrough therapy designation by the FDA. If approved, it would address the serious and debilitating unmet medical need, which is estimated to impact over 4 million people in the U.S. alone. Separately, we are also making progress on our development plans for AXS-05 for the treatment of smoking cessation and anticipate initiating a Phase II/III trial of AXS-05 in this indication this year. Moving on to AXS-12, our novel product candidate for the treatment of narcolepsy with cataplexy. We previously announced the completion of our registration program, which consists of three controlled Phase II and Phase III efficacy trials in a long-term safety trial. We continue to work toward our plan NDA submission, which we anticipate in the second half of this year. Despite the currently available treatment options, many patients with narcolepsy remain inadequately managed due to the heterogeneity of the condition and variable response and tolerability to currently approved agents. Based on the clinical data to-date, AXS-12 has the potential to deliver rapid and durable improvements in cataplexy while also demonstrating potential across other key symptom areas. Shifting now to our ongoing Phase III clinical development programs for Solriamfetol, which is being evaluated in ADHD, MDD, binge eating disorder and excessive sleepiness associated with shift work disorder. In the first quarter, we announced positive top-line results from the FOCUS Phase III trial of Solriamfetol in adults with ADHD. With these promising results in hand, we plan to initiate a Phase III pediatric trial for Solriamfetol in ADHD later this year. We also reported top-line results for the PARADIGM study, which was a Phase III proof-of-concept trial, evaluating the efficacy and safety of Solriamfetol in MDD with and without excessive daytime sleepiness or EDS. In the prespecified subgroup of patients with severe EDS, treatment with Solriamfetol resulted in numerically greater improvements in depressive symptoms. Based on these results, we plan to initiate a Phase III trial for Solriamfetol in MDD patients with EDS later this year. In parallel, we remain focused on advancing our additional Phase III trials of Solriamfetol in binge eating disorder and excessive weakness associated with shift work disorder with top line results from both studies anticipated in 2026. Lastly, in February, we announced positive top-line results from the EMERGE Phase III trial of Symbravo in migraine patients experiencing inadequate response to oral CGRP inhibitors. Results of this study reinforced the unique clinical profile and potential of Symbravo to provide meaningful efficacy to patients living with migraine. As demonstrated by these important milestones we have achieved across our commercial and pipeline programs, Axsome continues to execute with discipline and focus. While we are closely monitoring trade policy developments, including proposed pharmaceutical tariffs, we believe that any potential impact to our business would be immaterial. In particular, the vast majority of our commercial manufacturing takes place in the U.S. and Canada, including our primary production facilities for Auvelity and Symbravo, and we do not commercialize these products outside the U.S. Additionally, all intellectual properties related to Auvelity, AXS-05 and Symbravo are [dociled] (ph) in the U.S. We appreciate that this is a key focus area for investors. And it is challenging environments like today that truly underscore the depth, resilience and adaptability of our business. We look forward to providing more updates on our progress as we expect 2025 to be another catalyst-rich year. With potentially five marketed products, across six indications by 2026, we are in a strong position to continue delivering innovation to patients and significant value to shareholders. With that, I'll hand the call over to Nick, who will provide details of our financial performance.

Thank you, Herriot, and good morning, everyone. Today, I will discuss our first quarter results and provide some financial guidance. Total product revenues were $121.5 million for the first quarter, representing year-over-year growth of 62%. This consisted of net product sales of $120.4 million and royalty revenue of $1.1 million. Total product revenue for the comparable period in 2024 was $75 million. Auvelity net product sales were $96.2 million for the first quarter of 2025, representing 80% year-over-year growth. Auvelity net product sales for the comparable period in 2024 were $53.4 million. Sunosi net product revenues were $25.2 million for the first quarter of 2025, representing 17% year-over-year growth and consisting of $24.1 million in net product sales and $1.1 million in royalty revenue associated with Sunosi sales in out-licensed territories. Sunosi net product revenue for the comparable period in '24 was $21.6 million, consisting of net sales of $20.7 million and $900,000 in royalty revenue. Auvelity and Sunosi GTN discount for the first quarter were both in the mid-50% range and we anticipate GTN to remain in this range for the balance of the year. Total cost of revenue were $9.8 million for the first quarter of 2025 and $6.3 million for the comparable period in 2024. Research and development expenses were $44.8 million for the first quarter of 2025 compared to $36.8 million for the comparable period in '24. The increase was primarily related to the company's 4 Phase III trials in Solriamfetol, CMC costs for the planned launch of Symbravo and higher personnel costs, including noncash stock-based compensation associated with organizational growth. Selling, general and administrative expenses were $120.8 million for the first quarter of 2025 compared to $99 million for the comparable period in 2024. The increase was primarily related to commercialization activities for Auvelity, including the expansion of the sales force and higher marketing expenses, prelaunch activities for Symbravo and higher personnel costs, including noncash stock-based compensation associated with organizational growth. Net loss for the first quarter of 2025 was $59.4 million or $1.22 per share compared to a net loss of $68.4 million or $1.44 per share for the comparable period in 2024. The net loss in the first quarter of 2025 includes $26.2 million in noncash charges comprised primarily of $23.3 million in stock-based compensation expense, $1.5 million in acquisition-related contingent consideration expense and $1.6 million in intangible asset amortization. We ended Q1 2025 with $300.9 million in cash and cash equivalents compared to $315.4 million as of year-end. We believe that our current cash balance is sufficient to fund anticipated operations into cash flow positivity based on the current operating plan. I will now turn the call over to Ari, who will provide a commercial update.

Thank you, Nick. Axsome delivered solid commercial performance for Auvelity and Sunosi in the first quarter of 2025, despite market seasonality headwinds at the beginning of the calendar year. Auvelity led the market in TRx growth in Q1, with approximately 167,000 prescriptions, representing 76% year-over-year growth compared to the first quarter of 2024 and 5% sequential quarter-over-quarter growth. Auvelity was one of only two branded MDD agents with sequential brand growth in Q1. By comparison, the antidepressant market was flat compared to the first quarter of 2024 and declined by 2% sequentially. Nearly 26,000 new patients were prescribed Auvelity in the quarter, bringing the total number of new patients started on Auvelity since launch to more than 190,000. Auvelity use in the first line or first hit setting is approximately 50% in the quarter, reflecting balanced utilization of Auvelity for patients regardless of prior treatment experience. Our sales team successfully activated 4,100 new prescribers in Q1, with continued growth across both psychiatry and primary care settings. We're beginning to see the initial impact of our most recent sales force expansion on overall scripts and new patient starts, and we expect continued impact from the expanded sales team throughout the year. Auvelity coverage remained stable in Q1 with 78% of all lives covered across channels and 63% of lives in the commercial segment, based on ongoing negotiations, we expect coverage for Auvelity to expand and improve in 2025. Turning to Sunosi. Total prescriptions were over 46,000, representing 12% growth versus Q1 2024 and a decline of 4.8% sequentially. By comparison the weight promoting agent market increased by 4% compared to the first quarter of 2024 and declined 5% sequentially. Approximately 3,800 new patients started Sunosi in the quarter, bringing the total number of new patients started on Sunosi to approximately 85,000 since launch. Nearly 440 writers were activated in Q1 resulting in a total cumulative prescriber base of more than 14,000 health care providers since launch. Payer coverage for Sunosi in Q1 was stable with 83% of lives covered across channels. Finally, our launch preparations for Symbravo are progressing as planned, including the build-out of our sales team and the development of marketing messages, materials and programs. Feedback from health care providers since approval has been very positive due to the large unmet need that still exists in the acute migraine space. There has been a strong positive reaction to Symbravo's clinical profile with rapid and durable migraine pain relief that is safe and tolerable. It is multi-mechanistic approach that attacks migraine pain in a unique way relative to other approved agents and Symbravo's novel MoSEIC technology. We look forward to sharing additional details of our commercial launch soon. In closing, Q1 was a solid quarter that sets up Axsome for another successful year. Continued advancement of our commercial execution capabilities will support ongoing performance for Auvelity and Sunosi, while enabling a potentially strong launch for Symbravo next month. I will now turn the call back to Darren for Q&A.

Thanks, Ari. Operator, may we please open the line for questions.

Certainly, we’ll now be conducting a question-and-answer session. [Operator Instructions] Our first question today is coming from Leonid Timashev from RBC Capital Markets. Your line is now live.

Hi, guys. Thanks for taking my question and congratulations on the quarter. So maybe a multipart one. You've got a number of developmental agents in front of the FDA right now. So I wanted to focus on that. I guess what has your sense been from the FDA on recent interactions? Has there been any changes to the review teams or agency responsiveness? Or I guess in particular, any evolution on the messaging of what may be required for approval, especially for AXS-05 in Alzheimer's agitation? And then I guess, given that you have breakthrough designation for that agent, I guess how confident are you that you'll be able to get a priority review here? Thanks I’ll hop back in queue.

Hi, Leo, it's Mark. Good morning. So right now, engagement and dialogue with FDA is status quo for us, remain status quo. And then with respect to AXS-05 and AD agitation, no changes there versus what we discussed and the feedback we've received from FDA with respect to our planned sNDA submission. And I think you had mentioned that it does have breakthrough therapy designation and it is eligible for prior review. And that's something – that determination is made by the agency at the time of filing.

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

Yes. Two questions really. One is, can you just give us a sense of when you're going to kick-in the DTC advertising for Auvelity? I know that is supposed to happen sometime this year. And then second, the question is really about just the orexin coming in to the narcolepsy class and just how you think about your products sitting in as directions come in? Thank you.

Hi, Marc, it's Ari. Thanks for the question. Regarding DTC, we expect to launch a national campaign later this year. If you visit our website, you will see that we have a new creative campaign, but the national campaign launch will be a little bit later this year. Regarding orexin and AXS-12, we are very optimistic about AXS-12, the feedback we got in particular, most recently at AAN when we shared the SYMPHONY data in an oral presentation that it's a compelling option, daytime dosing, strong impact not just on cataplexy, but other symptoms of interest. And the orexins, I think, is enthusiastic and so, there's still questions just about the safety tolerability and it remains to be seen how those drugs will perform and sort of their late-stage products. So we're keeping an eye on it, but we think that there's a real market for AXS-12 in the short-term, and we look forward to getting it into the hands of providers and patients.

Thank you. Next question is coming from Andrew Tsai from Jefferies. Your line is now live.

Hi, good morning. Congrats on the execution. And thanks for taking my question. It's around Auvelity with your recent settlement with Teva for to 2039 time frame. Can you confirm if this is the absolute earliest that any generic out there can enter at this juncture? And does this settlement embolden you to pursue other opportunities outside of smoking cessation and agitation, assuming that you do have guaranteed run rate for at least 13 years. Can we expect more follow on indications soon? Thank you.

Hi, thanks for the question. This is Hunter. I'll answer the first part, and then I'll turn it over to Herriot for the second part. For the first part, Teva has a 180-day regulatory exclusivity. So regardless of what happens, Teva will be the first generic to launch. So other generics in file, but they would come in after Teva. And then I'll turn it over to Herriot.

Yes. And in terms of whether it emboldens us to pursue other indications, we have always planned to pursue other indications with AXS-05, given the pharmacology. So the nearest term new opportunities, Alzheimer's disease agitation, and we're on track to file the sNDA for that in the third quarter. And following that, we also have smoking cessation, and we are on track to initiate a Phase III trial in smoking cessation this year.

Thanks.

Your next question today is coming from Ash Verma from UBS. Your line is now live.

Hi, thanks for taking my question. For AD agitation, so thanks for providing the clarity that it will be in sNDA. Just curious, how does that impact the commercial potential here? I would imagine that you would have been more favorably positioned on GTN if it was its own NDA as opposed to getting lumped into depression, which now you're run rating at 55 -- mid-55 -- mid-50 gross to net.

Thanks, Ash, for the question. I think the sNDA does provide some clarity regarding promotion of AXS-05. It will share the Auvelity's name. As it relates to your question on GTN, I think that, that's one way of thinking about it. The other is that we expect, based on -- or existing payer contracts and the ongoing negotiation, there is a familiarity with the product and sort of the clinical profile overall has been very positive. So we think of this as being ultimately beneficial to helping secure access for the new indication. And so the GTN component, I'm not sure that we see it necessarily the same way, but ultimately, we need to get an approval for this indication and expand our existing contracts in order to secure access for the new patients. So we’re feeling pretty good about the sNDA. We think there’s some really nice advantages from a commercial standpoint, and we look forward to sharing some more in the future.

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

Thank you so much for taking my questions. Firstly, I was wondering if you could comment on your expected cadence of coverage for Symbravo following the launch rollout next month in terms of how quickly you expect Symbravo to reach qualitatively the same level of access that you currently have secured for Auvelity and Sunosi. And then secondly, I was wondering with respect to the additional indications for Solriamfetol, would you say that at this point, given the information you currently have that binge-eating disorder represents the most attractive opportunity from a competitive positioning standpoint? Or is one of the other indications still likely to be more attractive in terms of overall commercial value. Thank you.

Regarding coverage for Symbravo and the cadence, obviously we are focused right now on negotiations for Symbravo. I think it's premature to say exactly what the cadence would be, but we are focused on securing access as quickly as we can, understand it is a highly competitive market, but there is still significant unmet need and Symbravo's unique clinical profile, we believe, has significant advantages for patients and payers are seeing that clinical value. So I would say stay tuned for additional updates regarding market access on Symbravo.

Great. This is Herriot. With regards to the second question on Solriamfetol in the additional indications and how we see the product's positioned versus competitors. We really like the profile of this for Solriamfetol. We've announced positive results in ADHD. And while you can't make cross-trial comparisons and you'll always be careful about that because different trials are run in different patient populations. It was encouraging that the improvement from baseline in terms of the primary endpoint, the AISRS was one part with what is seen with currently approved stimulant agents. So we really like that. And obviously, there will be further characterization of the clinical profile in ADHD. As it relates to binge eating disorder, it is too early to make pronouncements there. Obviously, there is only one other product which is approved for binge eating disorder. So if Solriamfetol were to be successful, it will be the second product. So from a competitive perspective, that is a very nice dynamic to have. However, we have to wait to see what the results of the Phase III trial are.

Thank you.

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

Hi, good morning, Herriot and team, congrats on a good quarter. Thanks for taking our question. My first question is on Symbravo. I think Ari mentioned Symbravo launch coming up here in terms of building out the sales team. Could you give us any idea of kind of what that means in terms of number of persons or focus, would you perhaps focus on sites that are treating migraine and therefore, helpful to the rest of the portfolio? And then when do you anticipate being able to present some of the recent data on Symbravo, including responsive CGRPs. Could that be at the American Headache Society Meeting later in June?

Hi, Charles, thanks for the question. So regarding Symbravo selling effort, we are close to the completion of the build-out of that sales team. We expect to have approximately 100 sales representatives focused primarily on a highly concentrated group of acute migraine treaters and headed centers and large neurology practices. Your point about synergy with the existing portfolio is something that we are taking a close look at. There is some utilization in the psychiatric space, I'd say, the synergy is more pronounced than the primary care space. That's something that we will continue to evaluate for future promotional efforts.

So as you can imagine, AHS will be a very important scientific meeting for us, and we do expect to have presence there.

Okay. Great. Thanks.

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

Hi, thanks. Wanted to drill down more on esreboxetine and fibromyalgia. I know you talked about it. I'm wondering, number one how are you thinking about the sales opportunity. At one point over a decade ago, Pfizer was prioritizing LYRICA and fibro, Lilly was prioritizing Cymbalta in fibro. So there is a big opportunity. Lots of DTC. Of course, those products are generic now. So how do you think about the underlying opportunity, given on one hand, the size of the market, and on the other hand, the fact that there are generics of these products. So that's number one. And then number two, what's the extent to which you are going to expand the sales force to support esreboxetine? Thanks.

Yes. Thanks, David. We are very enthusiastic about AXS-14 and its potential impact. Fibromyalgia, as you mentioned, it is a large market. There are about 17 million people in the U.S. diagnosed with fibromyalgia. And so when you think about promotional efforts, the indication is treated by a diverse group of ACTs in rheumatology, primary care pain, neurology and psychiatry. When we look at the key focus is the concentration, specifically in rheumatology and primary care markets. We are continually evaluating the appropriate size and structure for the AXS-14 sales team, but we do believe there will be -- likely be a mix of utilizing existing sales teams, as well as adding additional sales efforts, particularly for the rheumatology space. And as it relates to consumer advertising, stay tuned for more information. We are evaluating the most effective way of engaging with patients. As you know, this is a long dormant market from a promotional standpoint. So we are looking at novel ways of engaging with patients in the future.

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

Hi there. Good morning. Congrats on the quarter. And thanks for taking my question. So first, I wanted to ask on Auvelity. Could you just give a little bit more color on your expectations for how payer coverage might evolve for the product over the course of this year? I think you have two major GPOs under contract and so just wondering if getting the third one would be key in your efforts to get the coverage you want. And then on Sunosi, could you give a little bit just any color you may have on how you're seeing the growth in the EDS for narcolepsy versus OSA indications? Thanks a lot.

Yes. Thanks, David. So regarding Auvelity, our team is focused on two primary objectives: increase the number of covered lives and reduced utilization management such as prior authorizations and step edits. We are pleased with the progress the team has made in negotiations across channels, and we do expect access to further expand and evolve this year and beyond. As it relates to Sunosi, we have seen really nice growth in both indications, but faster growth in the OSA indication. This is obviously a larger patient population. And based on our interactions with the HCPs, we've seen significant unmet need, particularly in this area where majority of our growth is coming from.

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

Hi, congrats on the strong quarter. Thanks for taking our questions. It's great to hear that you have the meeting minutes from the ADA pre-NDA meeting. Any color you can share on how the meeting went. And any notable surprises, if any? And do you plan to have any other meeting before the actual submission in 3Q? And just a quick follow-up. You are now in your third year of Auvelity launch. When do you think you'll be in a position to provide guidance on the Auvelity for MDD? Thank you.

Hi, Joon, I don't know that we have any additional color with respect to the engagement with FDA besides what we disclosed and we are excited about the data we have and our progress towards an sNDA submission. That remains on track. In terms of additional meetings and things like that. Right now the gating steps between today and the submission are completing build-out of the package. And so that's riding and compiling the module. So we feel good about the work ahead of us. We will keep you posted.

Yes. And Joon, it's Nick. As it relates to sales guidance, yes, we are in our third year. I would say still a pretty situation as Ari talked about earlier about payer coverage continuing to evolve. We just launched the field force expansion in Q1. We have the DTC campaign that's going to be occurring later this year. So all of these items will have a material impact. So I understood the question on sales guidance, but I still think it is a bit premature, but we'll direct you to our corporate website where we speak to the range of $1 billion to $3 billion for peak sales for MDD alone, and then larger than that for ADA.

Thank you. Your next question today is coming from Cerena Chen from Wells Fargo. Your line is now live.

Hi, thank you for taking my question and congrats on all the positive readout so far. I wanted to ask more about the strategic direction of the pipeline. As you have several assets pending regulatory review, how are you thinking about next steps? Would you say the focus is more on expansion opportunities? Or are there any plans for new molecular entities?

Thanks for the question. Right now, given the breadth of the pipeline and the number of assets that we have that are in late-stage development in any stage products, our focus is to make sure that we execute crisply. So we want to make sure that we execute on these opportunities, which if you look at all the opportunities given the stage of development in the patient population, has the potential to deliver peak sales of north of $16 billion. So we want to make sure that we execute and take those over the finish line. Having said that, there are other opportunities, which are always being presented to us as well as opportunities currently internally, which we have not disclosed. And stay tuned for those, and we will disclose them as they mature or as they become appropriate.

Thank you. [Operator Instructions] Our next question is coming from Vikram Purohit from Morgan Stanley. Your line is now live.

Hi guys. Thanks for taking our questions. This is Pat on for Vikram. Could you comment on your intended design of the Phase III study point to initiate later this year for Solriamfetol and MDD with EDS, like how large of a study population do you anticipate? And what do you see as the key endpoints here? And lastly would this be the only additional trial required for potential approval?

Thank you for the question. What we've done historically is disclose the exact design of the studies once we've launched them. Now we really like what we saw in terms of a signal in this patient population, that is patients with MDD and excessive sleepiness. As a reminder, that represents probably around 50% of patients who have MDD. We will take all the learnings from the study, which we've completed as well as the learnings from other depression trials, which we've conducted with our other products as we think about the design of this next study.

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

Hi, good morning. Thanks for taking my questions. Just a follow up on the MDD EDS opportunity. Just trying to get a sense of how confident you are that, that really is half the MDD population, given the subgroup was only 15% of the study population? Was there anything specific in the enrollment criteria that maybe restricted the enrollment of EDS comorbid patients? And then with respect to your MDD peak sales, $1 billion to $3 billion, when do you think you'll be in a position to narrow that guide? I'm just kind of wondering, as you guys think about where you sit today, maybe what are some of the key variables that push you to the high end of three versus maybe the $1 billion peak sales range. Thanks.

Sure. As it relates to the MDD in EDS indication, in the study which we completed, we wanted to see if there was a signal and to ensure that we had great sensitivity as well as specificity, but importantly, specificity. We define the [indiscernible] patients with severe EDS. Now if you look at patients who have EDS with MDD, it is about 50% of the population. And in terms of the MDD peak sales potential of more to $3 billion that does incorporate a lot of different variables. One of the things to watch is what the trajectory is of our current sales. And as we continue the launch and as other aspects evolve, we might be in a position to narrow guidance. But right now, we feel that, that is a very achievable range. And certainly, the low end of that is very achievable.

Thank you. Our next question today is coming from Joel Beatty from Baird. Your line is now live.

Hello. Good morning. This is Chris on for Joel. Just a couple of questions on Symbravo. How are you thinking about that CGRP data in February in terms of -- are you going to pursue that in a new indication or a label expansion? And then is the plan still to pursue Symbravo, expand the label as well in adolescents? Thanks.

Yes. Thanks, Chris, for the question. From the CGRP data in the EMERGE study, which we read out earlier this year. Obviously, it is a very compelling data. We've been able to share it in the market since we received it. And it is very clear that clinicians are motivated by that data as it gives them an additional place to try Symbravo once it's commercially available. At this time, we are not seeking to add it to the label as a new indication but we'll look to promote it through CSL guidance that the FDA puts forth and obviously, through our medical affairs team in medical education.

I can take the last part on pediatric development. That work is underway as agreed to with the FDA. So stay tuned for updates there.

Our next question today is coming from Graig Suvannavejh from Mizuho Securities. Your line is now live.

Hi, good morning. Congrats on the progress. Thanks for taking my question. Maybe just a bigger picture question on profitability or tantalizingly close to being a profitable company given where you are in cash and kind of where cash has evolved over the last several quarters. Just any comments on whether you do think that profitability can be achieved in 2025, at least on a quarter basis? Thanks.

Thanks, Graig. As you know, we haven't provided any guidance around timing, but we do remain confident we'll get the cash flow positivity with our current cash that is on hand. We are -- we expect to see, in 2025 leverage in our P&L, so a bit in Q1 already as sales growth is outpacing our operating expenses. And I think it is important we build Axsome on a very disciplined approach in how we are investing in our operations and how we allocate across our portfolio. On the R&D side, the vast majority of our investment today is in our late-stage pipeline, late-stage programs and where we expect a high rate of return on that investment. And on the SG&A side, we've built significant infrastructure over the past three years, initially support Sunosi and Auvelity in now providing operating leverage as we launch Symbravo for future product launches. So we believe that we kind of summarized that the current cash will take us to cash flow positivity. We haven't given any specific guidance around profitability, but we feel like we're on the right course.

And then maybe just as a quick follow-up, Nick, just on the evolution of your R&D and SG&A. R&D did come down relative to the fourth quarter. I don't know if you expect that to be sustained in terms of where R&D is right now. I would assume SG&A would tend to tick up higher, but just if you could provide your comments there would be appreciated. Thanks.

Yes, sure. Yes, you're right. R&D did tick down a bit from Q4. Three ADA trials were completed in Q4 and then the ADHD and MDD trials were completed mid quarter in Q1. We would anticipate R&D spend to increase from the Q1 level as we initiate our second Phase III for Solriamfetol in ADHD and MDD with EDS. Additionally, as a reminder we did file the NDA for AXS-14 in Q2, so we will have that filing fee in Q2. And then as for SG&A, we do expect to see an increase versus Q1 as we complete our hiring for the Symbravo team, the Symbravo field team. We did have in Q1, a partial quarter of leadership team higher and Q2 will also include a partial quarter of the sales team for Symbravo. So we would anticipate that to tick higher in Q2. And then as Ari talked about, the DTC campaign later in the year, that will further increase SG&A.

Thank you. Our next question today is coming from Yatin Suneja from Guggenheim Partners. Your line is now live.

Hi guys. Thank you for taking my question. The question is on the ADHD study that you had recently announced. Could you just talk about the path forward there? Also, I think at that time when you announced the data, there were some questions around the 300-milligram internal [indiscernible]. If you can just talk a little bit about why was that used, you had earnings from that 300-milligram dose going forward? So that's one. And then the second one is on Auvelity in terms of the coverage there. I think it seems like some plateau in terms of the coverage, at least on the commercial side. Could you just talk about what is an ideal number to reach right now since like you are at about 60%, 65%?

Yes. We'll start with the second question. We were having some difficulty hearing you on the first one, so maybe just clarify. But the -- regarding coverage, obviously, we've had -- this coverage has been stable over the last couple of quarters, but we have been actively negotiating and in communication with payers. And so we expect the access to expand and evolve this year. In terms of ideal percent of covered lives, obviously, we want to secure as many covered lives as possible. There is not a specific number that we have in mind, just ultimately really focused on improving access for patients so that more patients have the opportunity for coverage with their health insurance plans.

Great. And Yatin, as it relates to the first question for ADHD, the path forward is to initiate and complete the Phase III trial in pediatric patients. With regards to the [indiscernible] study and the 300-milligram dose, as a reminder of the top dose, which is approved for Solriamfetol is 150 milligrams per day. Given that this was the first study that we are conducting in ADHD, we did want to look at a higher dose just to make sure that we define what those response was. Now the 150 milligram dose, that was primary dose of focus, that's the highest of good dose, very happy with the results of the study which showed a very clear treatment effect for that dose.

All right. Thank you.

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

Yeah thanks for taking the question. Congrats on the quarter. I think on May 24, we're expecting the Make America Healthy Again Commission to release an initial report on prevalence and threat of SSRIs antipsychotic mood stabilizers stimulants, kind of a catchall. And I think it's actually maybe focused on childhood disease. But question is, if you had sort of any interaction with the commission on that report as it pertains to Auvelity or Sunosi? And I think they're going to finalize it in August. So do you expect to be able to comment on that one? That's the first question. The second is just on narcolepsy. I think a few of the other KOLs we've talked to are like, look, the efficacy for AXS-12 looks great on cataplexy. There is some other symptoms that it looks interesting on as well. But in terms of the stimulant effects, they are looking for like maintenance of wakefulness test. And I'm wondering whether you're going to have that data in the open-label extension? Thanks very much.

With regards to the first question, we have not had any interactions with the commission, and we're going to stay tuned, just like everybody else to see what the outcomes are as we state as we make sure that we keep an eye out and keep an ear out for anything that comes out that might affect the sector. As it relates to AXS-12, so with regards to the [BMWT] (ph), we have not incorporated BMWT our open-label trial. So however, we have looked at excessive sleepiness, as you know, using other measures including the clinical global impression severity.

Thank you. Next question today is coming from Troy Langford from TD Cowen. Your line is now live.

Hi, thanks for taking the question and congrats on all the progress this quarter. Just one on Sunosi and ADHD, just given the level of efficacy that we saw in the Phase III ADHD study not too long ago, do you have any reason to believe that the Phase III pediatric study will show a substantially different level of benefit? And then just a follow on to that, do you all have any expectations for approximately how long that pediatric study could take?

What we know is that historically, there is no correlation between efficacy for ADHD in adults as well as ADHD in pediatric subjects. So we like the fact that we have now seen a clear effect in adult population. However, we need to conduct the study in pediatric patients. And then in terms of the – how long it would take to enroll that study and conduct it is premature. So what we’ll do is we’ll provide some guidance, generally speaking, once we launched the study and talk about the exact design.

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

Hi, thanks for taking my question. Just maybe stepping back with a lot of your assets in late stage or in-market. Can you talk about how you are managing the business in terms of operating margins and investing across these various assets relative to also exploring potentially bringing in any additional assets? And how do we think about what would be sort of that return on investment decision that you make and then driving into kind of that path to profitability? Thank you.

Sure. Thanks, Ami. As I mentioned earlier in my comments, a lot of our focus, a lot of the R&D spend is on late-stage programs. And that has a high POS and a high rate of return. So we continue to invest in that. As I mentioned, R&D was slightly down for the quarter versus Q4, but continue to invest in developing those late-stage programs. And the infrastructure that we have built over the last three years, specifically starting with Sunosi and then with the launch of Auvelity, we are able to leverage that infrastructure on all of our future programs. So we believe that from that perspective, that those programs will have a higher ROI.

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

Well, thank you all for taking the time to join today's call. As you've heard today, Axsome has accomplished a great deal in the first quarter. We are up to deliver another impactful year driven by strong commercial execution, we're rapidly expanding portfolio and multiple upcoming milestones. We appreciate your continued interest and support as we continue our work to bring innovative new treatment options to patients and create long-term value for our shareholders. Thank you very much.