AXSM - NASDAQ

Good morning, and welcome to the Axsome Therapeutics Third Quarter 2024 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Later, there will be a question and answer session and instructions will be given at that time. Please note that today’s call is being recorded. I will now turn the call over to Darren Opland, Director of Corporate Communications. Please go ahead sir.

Thank you. Good morning, everyone and thank you for joining our third quarter 2024 financial results conference call. I am joined today by Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Mark Jacobson, Chief Operating Officer, and Ari Maizel, Chief Commercial Officer. Earlier this morning, we posted a new corporate presentation complementing today’s call to the Investors Section of our website. Those joining by webcast may also again see the slides at any time during the discussion. As a reminder, 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, 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, our commercial plans regarding Sunosi, Auvelity, and our pipeline products, revenue projections, and other financial forecasts if any, and the possible intended use of cash and investments. These forward-looking statements are based on current information, assumptions, and expectations of future events and are subject to certain risks and uncertainties that may cause the company’s actual performance and results to differ materially from those projected. Please refer to today’s press release, presentation, and our SEC filings for additional details on these and important risk factors. You are cautioned not to rely on these forward-looking statements, which are only made as of today's date and the company disclaims any obligation to update or revise these statements. With that, I’ll hand it over to Herriot.

Thank you, Darren, and Good morning everyone. Thank you for joining us on today’s financial results and business update conference call. At Axsome, we are focused on developing and delivering novel, innovative medicines that can transform the life of patients living with serious central nervous system conditions. We are pleased to report on the progress we’ve made in advancing this important mission in the core, particularly, our long-term vision, and review potentially value-driving year and intermediate term milestones. The third quarter was another strong quarter, it represented another novel milestone as we delivered quarterly product revenue in excess of $100 million for the first time. This quarterly performance translates to an annual revenue runrate of approximately $420 million, just three quarters into our second full year as a commercial therapy. While this progress is tremendous, even more significant patient growth lies ahead, based on our current portfolio of innovative marketed and late-stage pipeline candidates. In addition to Auvelity and Sunosi, our two FDA approved treatments for major depressive disorder and excessive daytime sleepiness and narcolepsy start to sleep apnea respectively, our pipeline features five innovative late-stage product candidates currently in development, and nine indications across psychiatry and neurology. Our late-stage pipeline positions us to continue to deliver important new medicines in therapeutic areas that impact more than 150 million patients in the US. If successfully developed, this portfolio has the potential to provide over $16 billion in peak sales. The diversity and depth of our pipeline also reflects Axsome’s differentiated approach to scientific innovation, which we believe aligns with our patient-centric mission and expand the therapeutic possibilities for CMS conditions. Now before turning it over to Nick and Ari who will provide clear detail on the strong performance in the quarter, for Auvelity and Sunosi, I will provide an update on the pipeline and upcoming milestones. A key development in the quarter was the resubmission of our new drug application for AXS-07, our novel, multi-mechanistic product candidate for the acute treatment of migraine. The resubmission was acknowledged by the FDA and designated as a Class 2 resubmission with a PDUFA action goal date for January 31st, 2025. Launch preparations are underway to ensure timely commercialization if approved. Our ongoing EMERGE Phase 3 trial, evaluating the AXS-07 in patients with a higher inadequate response, the oral CGRP antagonist is on track to read out in the fourth quarter of this year. Results from this trial will help inform the potential utility of in excess of AXS-07 in different patient subgroups. With respect to AXS-02 for the management of fibromyalgia, we are completing incorporations for the NDA submission and expect to submit the NDA to the FDA this month. I'd now like to comment on our other late-stage pipeline products starting with the AXS-05. Our comprehensive development program for AXS-05 and Alzheimer’s disease agitation consists of four pivotal Phase 3 placebo-controlled efficacy trials. The completed positive ADVANCE-1 and ACCORD-1 trials and the ongoing ADVANCE-2 to and ACCORD-2 trials. ADVANCE-2 is a parallel group trial and ACCORD-2 uses the randomized control design. Given that target enrollment in both trials have been reached, we are on track to report topline results from both ADVANCE-2 and an ACCORD-2 simultaneously this quarter. We look forward to these readouts as we believe that a favorable outcome from one or both of these ongoing pivotal studies in addition to the positive results from the two completed trials would provide strong support for an NDA filing for AXS-05 for Alzheimer’s disease agitation. Starting now to AXS-12. We are currently conducting a two period Phase 3 trial evaluating the long-term efficacy and safety of AXS-12 in narcolepsy called the ENCORE for evaluating continued treatment with our opportunistic studies. The trial consists of a 24 week open-label period followed by a 3-week double blind, randomized withdrawal period. Enrollment in the trial is complete and we are on track to report top-line results this quarter. The ENCORE trial is conducted as a registrational study to provide additional support for our planned NDA for AXS-12. Following completion of the trial, we plan to request a clearly meeting with the FDA to discuss our planned submissions. Rolling our development pipeline, we continue to advance our four ongoing Phase 3 trial of solriamfetol in ADHD, major depressive disorder or MDD binge eating disorder and shift work disorder, which we believe represents significant expansion opportunities for solriamfetol. Enrollment in the FOCUS study, our Phase 3 double blind placebo-controlled trial evaluating the efficacy and safety to solriamfetol in ADHD in adults is expected to complete in December. And as a result, we now expect to see top-line results in the first quarter of 2025. Additionally, the PARADIGM Phase 3 trial in major depressive disorder is to recognize sleep with enrollment also expected to complete this quarter. PARADIGM will examine the effect of solriamfetol in MDD patients with and without excessive daytime sleepiness. We now anticipate top-line results in the trial in the first quarter of 2025. Lastly, the ENGAGE Phase 3 trial in in binge eating disorder and a SUSTAIN Phase 3 trial in shiftwork disorder continue to enroll with top-line results anticipated in 2025 and 2026 respectively. As we highlighted in previous calls, solriamfetol’s unique pharmacology and we don't believe in[Indiscernible] in top-line in 5ht1 agonist along with preclinical and clinical evidence support its potential to treat a broader range of CNS conditions impacting over 80 million people in the US. With the potential new indications for solriamfetol under study, we have the potential to deliver multiple, value-creating catalysts to drive long-term growth for solriamfetol alone. In closing, the path ahead for Axsome includes, a robust series of clinical, regulatory and commercial milestones with strategic focus, operational excellence, a strong balance sheet, we are confident in our ability to deliver significant near and long-term value for patients and shareholders. With that, I’ll hand over to Nick.

Thank you, Herriot. Today, I will share our third quarter financial results and provide some financial guidance. We delivered yet another robust quarter and recorded total net product revenue of $104.8 million, compared to $57.8 million for the same period in 2023, representing an 81% year-over-year increase. Auvelity’s strong sales momentum continued with net product sales increasing to $80.4 million in the third quarter, representing a 113% growth, compared to the prior year period and 24% sequential growth versus Q2 2024. We are also pleased with the continued performance of Sunosi, which delivered net product revenue of $24.4 million in the quarter or a 21% increase, compared to the same period in 2023. Gross to net was approximately 50% for Auvelity and in the low 50s for Sunosi. Our R&D expenses for Q3 were $45.4 million, compared to $28.8 million for the same period in 2023. The increase was primarily driven by our ongoing clinical programs for AXS-05 and solriamfetol, as well as increased chemistry, manufacturing, and controls costs associated with our pipeline products and higher personnel costs including non-cash stock-based compensation associated with organizational growth. SG&A expenses for the third quarter were $95.6 million, compared to $83.2 million for the same period in 2023. The increase was mainly a result of continued investments for the commercialization of Auvelity and Sunosi, along with higher personnel costs, including non-cash stock-based compensation associated with organizational growth. Net loss for the third quarter was $64.6 million or $1.34 cents per share, compared to $62.2 million or $1.32 per share for the comparable period in 2023. The $64.6 million loss includes $40.9 million in non-cash charges which reflects a fair market value adjustment for contingent consideration this quarter of $16.4 million. Cash and cash equivalents totaled $327.3 million as of September 30th,, 2024. As we approach the potential launches of AXS-07 in migraine and other late-stage assets in the coming years, we remain committed to our principal, efficient approach to capital allocation that has yielded substantial returns to-date. As such, we believe that our current cash balance is sufficient to fund anticipated operations into cash flow positivity, based on the current operating plan. And with that, I'll turn the call over to Ari, Axsome’s Chief Commercial Officer to provide details on our commercial performance.

Thank you, Nick. Axsome delivered robust commercial performance in the third quarter of 2024. In addition to strong sales performance for Auvelity and Sunosi, Q3 saw continued improvements in market access dynamics, for both brands, including an increase in covered lives for Auvelity for the second consecutive quarter, reinforcing strength and quality of our commercial execution. Auvelity once again outperformed the market in branded competitors with approximately 144,000, prescriptions in the third quarter, representing 108% growth year-over-year and 17% growth sequentially compared to the second quarter. By comparison, the anti-depressant market grew 1% year-over-year and sequentially. Nearly 26,000 new patients were prescribed Auvelity in this quarter, bringing the total number of new patients started on our Auvelity since launch to nearly 140,000. Our sales team successfully activated more than 4,100 new prescribers in the third quarter and continues to penetrate both the psychiatry and primary care markets among MDs, NPs and PAs who care for the majority of depression patients across the US. On the market access front, our previously announced expansion of covered lives for Auvelity resulted in meaningful increases in new patient starts and covered claims. Coverage continues to evolve and expand and Auvelity now has 63% of commercial life covers and 78% of total lives from across their channels, Negotiations with payers and PBMs are advancing across the access landscape. To build on the success of the Auvelity launch, we are planning a second expansion of our Auvelity, psychiatry sales force to approximately 300 sales representatives, which is expected to complete in the first quarter of 2025. The increase in share of voice combined with strengthened market access, outstanding product attributes, and positive provider and patient experiences with Auvelity will position the brand for further growth as we enter another pivotal year for Axsome. Turning to Sunosi. Total of prescriptions were approximately 47,000 in the quarter, representing 15% year-over-year growth and 5% sequential growth. By comparison, the weight promoting agent market grew 3% year-over-year and 4% sequentially. Sunosi had strong performance with new patient prescriptions once again in Q3, with more than 4,100 new patients initiating Sunosi treatment during the quarter as the Sunosi team continues to drive depth with existing prescribers while also activating approximately 400 new writers in the quarter. Turning now to AXS-07. As Herriot mentioned in his open, we are eagerly anticipating the January, 31st PDUFA date for this Innovative treatment. Migraine is the leading cause of disability among neurological disorders and affects approximately 39 million Americans, 70% of whom report not being fully satisfied with their current treatment due to sub-optimal efficacy. If approved, AXS-07 distinct multi-mechanistic pharmacology has the potential to address this unmet need. Launch preparations are well underway, including the buildout of the AXS-07 sales team. We anticipate a commercial launch in the first half of 2025. In closing, we have made significant progress in 2024, our second full year as a commercial company in a firmly established Axsome as a trusted partner for providers, patients, and payers, providing a solid foundation for continued commercial performance for Auvelity, and Sunosi, as well as future product launches. I will now turn the call back to Darren for Q and A.

Thanks, Ari. I'll now turn it over to the operator to begin Q&A.

Thank you. [Operator Instructions] Our first question comes from Vikram Purohit with Morgan Stanley. Please proceed with your question.

Hi, everyone. This is Morgan on for Vikram. Thank you for taking our questions. So, on the Auvelity sales force expansion, how long would you expect this full expansion to take? And how much of a sales lift would you expect from the expansion? And then I have a follow-up after that. Thank you.

Hey, Morgan. This is Ari. Thanks for the question. As we mentioned, we expect the expansion to be completed in the first quarter of next year. In terms of lift I would suggest that our last expansion, the guidance we gave was that the ramp would build over the course of the year. I think you saw as we completed our expansion in January of this year, we started to see the impacts straight away and it's been part of the reason why the brand has performed so well over the course of this year. So we would expect a similar impact for the second expansion.

Okay. That's helpful. Thank you. And then, would you say how much of this move would be driven by the desire to expand in MDD versus preparation for a potential ADA launch, as well?

And this is really about MDD and the rationale for it, recent market access wins would expanded the potential for Auvelity and of course our second-line treatment. We've also seen promising growth in the primary care market. We expect further improvements in market access moving forward and continued growth in primary care. So this makes sense to capitalize on those dynamics. But to your point, we do see potential synergy after the future if ADA is approved and so we’ll share more updates on that at appropriate time.

Thank you.

Our next question comes from Jason Gerberry with Bank of America. Please proceed with your question.

Hey guys. Thanks for taking my questions. First is on Auvelity curious your thoughts on new atypical antipsychotics that are likely to be approved next year. As adjunctive I get that these are technically considered different segments of the market. But, is it fair to think that the target patient that might be an option for a new monotherapy with a different mechanism versus considering going on to adjunctive there is sort of a competitive tension there. So, I'm just wondering if these new – I knew atypical CAPLYTA with a better tolerability profile might be somewhat of a competitor to Auvelity? That’s my first question. And then just as a follow-up, on the ADA marketplace, I know in the past you guys have said, you feel like you have a differentiated profile. So whatever we're seeing with Rexulti may not be applicable to an eventual Auvelity launch. But I guess the one thing we've heard is the big issue has been high out of pocket cost for patients, because it’s a high Medicare SKU. Sponsors aren’t really able to defray those costs through co-pay assistance program. So, how do you overcome that hurdle which seems more intrinsic to the ADA marketplace? That’s my follow-up. Thanks.

Great. Yeah, no, thanks. Jason for the questions. Starting with the atypical question, yeah, obviously adjunctive MDD is slightly different than monotherapy MDD. And although there is use of atypicals in addition to monotherapies, we do see these at distinct marketplaces. As we've stated previously, we firmly believe that Auvelity is the first or second-line treatment, typically atypical will come into play in later life third to four and the patient has had inadequate response to a monotherapy treatment. You're comment about CAPLYTA’s tolerability profile I believe is related to other atypicals, because safety tolerability profile would say is, is very strong in this marketplace. So while we expect there to be some level of noise, ultimately, we believe our key competitive set is with monotherapy SSRI, SINRIs and that's how we're commercializing the products. As it relates to ADA, we have been following the Rexulti launch very carefully. And I think, for any branded agent on the marketplace, out of pocket expense is always a top concern for providers and patients. Part of our strategy is to continue to develop strong working relationships with payers and TDMs across the landscape, as we develop those relationships and expand coverage for Auvelity and Sunosi, we expect there to be benefited for the ADA launch which should set us up to help mitigate out of pocket expenses for the patients over time.

Thanks. So you guys wouldn’t expect to have sorted all out of pocket kind of co-pay costs borne on these patients?

Jason, it really depends on the coverage and the rebate agreements that we have with the plan. So it's a little premature to comment exactly on the out of pocket expense, but our goal is to ensure that there's access for every patient and that out of pocket expenses is managed appropriately.

Got it. Thank you guys.

The next question comes from Leonid Timashev with RBC Capital Markets. Please proceed with your question.

Hi guys. It's Leo. Thanks for taking my questions. Congratulations on the quarter. Just a simple one from me I guess. On ADA, is that your reach target enrollment in both ADVANCE 2 and ACCORD 2? Can you talk about both how the patients you’ve enrolled in ADVANCE 2 compared to ENHANCE 1 and what your expectations would have been? And then also the event rates for ACCORD 2 compared to your expectations? Thanks.

Thank you for the question. So you mentioned, we have reached target enrollment and as it relates to the patient population, they're very similar. So, you are increasing the next crucial criteria for the ADVANCE 1 and ADVANCE 2 study or very similar. And I would say the same thing with regards to the ACCORD 1 and ACCORD 2. The goal was to make ADVANCE 2 as well as ACCORD 2 replicative studies. As it relates to the event rates, and the event rates are what we're expecting them to be and that is why, we're confident that we will be able to have readout this quarter for both the ACCORD 2 study as well as the ADVANCE 2 study simultaneously.

Our next question comes from Charles Duncan with Cantor Fitzgerald. Please proceed with your question.

Hey, morning Herriot and team. Congrats on a nice quarter and appreciate all the color on the pipeline. Lots going on. I had couple of questions. One is kind of commercial on AXS-05 and then a follow-up in terms of the pipeline and its upcoming readouts. With regard to Auvelity, are you getting more traction with Sykes or PCPs? And is the rapidity of response a driver to that? And do you think that that profile could read on potential differentiation relative to say, Rexulti if the drug shows effects and is approved for ADA? Thanks.

Hey Charles. This is Ari. Thanks so much for the question. To answer your question, we're doing quite well in both the psychiatry and primary care markets. That said in Q3, primary care clinicians was the fastest growing segment, which is a really great signal. It’s something we talked about historically that we've expected that segment of the market to continue to grow. So we're really pleased with the progress that we're making in the primary care segment. Your comment about rapid acting is spot on. It is one of the top drivers of utilization in the depression market. And yes, based on our early conversations with KOLs in the Alzheimer’s agitation market, that rapidity of responses are very compelling attributes that we think will be a core part of our brand story if launched.

Helpful. Thanks, Ari. Relative to the upcoming AXS-05 readout, it looks like ADVANCE 2 is slightly smaller sample size than ADVANCE 1. So does that make you at all concerned about what you might observe there in terms of effect size. And then, can you provide us any color on the ongoing open label extension study in terms of enrollment, our rollover into that and then persistence?

Great. So with regards to the sample size for ADVANCE 2, Charles, so the sample size is that you see in our slide presentation these are our target enrollment numbers. And the numbers always differ slightly. Once you actually complete enrollment, you never reach the exact numbers, you might usually it’s plus, or minus. So I wouldn't read too much into that except, uh, which of that number and use it as a guide to how the study is powered. In terms of the open label extension, we've seen a very nice, or very high percentage of patients rolling over from the control study into the open label extension sites. Or new clinical extension study and usually that's a positive sign in terms of how patients and caregivers perceive a product. So, we're very happy to see that. Another benefit of a high enrollment rate is the open label safety extension study is that – is that that will have us to move towards our target exposure numbers which I alluded from an ICA’s perspective to enable an NDA filing. And on that front, we're very well positioned.

Okay. Excellent. Thanks for the added color, Ari.

Our next question comes from Cerena Chen with Wells Fargo. Please proceed with your question.

Hi, thanks so much for taking my question and congrats on the strong quarter. I want to ask about the solriamfetol in ADHD with the FOCUS study now pushed out to 1Q ‘25. I was just wondering if there was any kind of slowdown or competition and enrollment. And then, what is your thinking on running the pediatric study? Are you still planning to start that prior to or potentially after the adult data readout? Thank you.

Hey Cerena, good morning. This is Mark. So with respect to timing that that’s simply the final screening funnel inside of what we're seeing. So the study is already over 95% enrolled. This is just our final estimate of how long the final patient enrollment study takes. So stay tuned and that's all I'm going to be getting along and then with respect to the Pediatric study, those those plans are in the works. And we're going to watch that as basically as soon as we're able to. And so also stay tuned for that. But it's not predicated on the FOCUS study, per se.

Thank you.

Our next question comes from David Amsellem with Piper Sandler. Please proceed with your question.

Hey thanks. So, wanted to ask about the cost structure, broadly speaking. And, I know, I'm not asking for any sort of guidance question about 2025. But I did want to drill down on how are you thinking about R&D spend not just for next year, but as you think beyond that, particularly with a lot of programs, a lot of studies wrapping up next year. How should we think about that? And then, secondly, regarding promotional spend and I know you have the expansion of the sales force in support of Auvelity. But how are you thinking about say migraine and then Alzheimer's and the extent to which you're going to be adding headcount to support these additional opportunities? Help us understand how SG&A is going to expand next year and beyond? Thank you.

Maybe I'll just give just some of the working comments and then, let the other members of the team provide more details. But just overall the way that we thought about spending, in terms of whether it's for R&D or for commercialization is to approach it in a very rational way. So, there is an intense focus in the company, culturally on return on invested capital. So everything that we do, will be very well thought out and will be done in a rational way. Now that may differ from what, maybe you used to see with other companies. However, think that that's the right way to run the business.

Sure. Yeah. And maybe just – hey Dave, this is Nick. And just to add on to Herriot I think he made the key points, but we as – as per right now at the end of Q3 are the strongest capital position that I'd say we've ever been since inception. As a reminder, with our current cash on hand, we have the ability to get to cash flow positivity and execute on all of our priorities that are in our operating plans, including further investing and Auvelity Sunosi, the launch of the AXS-07 and just furthering our pipeline. And then, just maybe specifically on this quarter, in Q4 and how we should think OpEx in Q4. We saw Q3 we had a decrease in R&D and SG&A in the previous quarter. We would expect this slight increase in Q4 as relates to R&D spend. And that's mainly due to the PDUFA for AXS-014 a week going shortly, and then SG&A. Again, potentially slightly increasing just as we prepare for the migraine launch.

Okay. Thanks for that.

Our next question comes from Marc Goodman with Leerink. Please proceed with your question.

Yes. Good morning. First of all on Auvelity, can you just give us a sense of how the product is being used and how that's evolving? Second question is, that expansion in the sales force, is that’s just for Auvelity? And how are the reps going to be used for the migraine launch? I know the question has been asked a few times, but just I'll ask it again, like, are we going to have another expansion for the migraine when its approved? Or are we going to leverage these reps that you're about to add? And then just lastly on Reboxetine, can you just give us an update on what you need to file this product You're running another study. You have the positive study. So, do you need this study? Is it positive to file or are we looking for more patients for long term safety? Just curious that the gating issue there is. Thanks.

Hey Mark, it's Ari. I'll start with the Auvelity utilization. So we again saw a incremental increase in first and second line use. It remains around 50% of first or second line use in Q3. So pleased with sort of the incremental growth and we expect that to continue to build particularly as we bring more market access online for the product. In addition, when you think about monotherapy or agile use, again we saw an increase in monotherapy use, but it remains around 50% monotherapy agile. So, overall, the trends are in line with our expectations. We expect that to continue to improve over time.

As it relates to the Reboxetine question, So Marc, I think what you are referring to is our ENCORE trial. This is a Phase 3 trial in patients with narcolepsy. So, we do not need this study to be positive in order to be with the file an NDA. So we already have our Q studies which will support the efficacy plans that we want to make with regards to Reboxetine AXS-12. However, the Phase 3 trial - the long term, the Phase 3 long-term safety extension trial, it doesn't cooperate in a three week randomized withdrawal period. So that's always been design of the study from the very beginning. And it's just that there has not been much focus on it. So, every year, the readout for that study we didn't want to point out that this is in fact, a controlled study and it should provide additional efficacy data and if it's positive that that's fantastic, it will make for in this stronger package.

But you are filing anyway with or without a positive study?

Correct. And the ENCORE study it has two periods. One is the open label period. That is six months, say, open label it’s extension file. So that is the original reason for running the study. So we do need that part of the study in order to file. And then using our strategy that we used in the past, which is to make sure that that more efficient and everything that we do when we design a study we did include a double-blind Phase, which is AXS-12 plus placebo.

Thanks.

Our next question comes from Joseph Thome with TD Cowen & Company. Please proceed with your question.

Hi there. Good morning. Congrats on the progress. And thank you for taking my questions. Maybe the first one on solriamfetol in MDD. I guess, given sort of the high bar that Auvelity has set in the indication, what sort of the area for differentiation that you are looking for here to consider additional investment on that program? And then, second, when you're thinking about the enrollment of AXS-05 in the Alzheimer’s agitation, where are you finding these patients? What sort of the last touch point before being referred into the studies? Is it a nurse - is it a Alzheimer's physician? Is it a primary care doc? Kind of where can we find the patients? And is it different in the commercial setting? Thank you.

Well, thank you for the question. As it relates to solriamfetol in major depressive disorders, so we are studying solriamfetol in patients within MDD both with and without excessive daytime sleepiness. So if you look at the drug from a pharmacology perspective, it has a novel mechanism of action which is a deep TAAR1 receptor agonist.. That provides the marketplace to the clinicians and end patients brand new mechanism of action in MDD and that MDD is a very heterogeneous patient population to have different mechanisms of action is they're useful. It was still in that first hand with Auvelity with its novel mechanism of action and how that has been received by the marketplace. As it relates to other points of differentiation, one of the – one of the clinical aspects of major depressive disorder is its association and comorbidity with excessive daytime sleepiness. So, that is one of the areas that we would look to explore in the PARADIGM study. So stay tuned and we are looking forward very much to learning from that study about the potential profile of solriamfetol and MDD. And, the other question which you ask related to Alzheimer’s disease agitation and where those patients are coming from? The way that that clinical studies are run is - we and another company partner with clinical file centers that that specialized in in psychiatry. So the way that clinical trial enrollment works is not to go specifically to the general population although there is advertising. It needs to go to centers that have experience and relationships between therapists patients and enrolling them. So that's where that that's where the patients are coming from. And as it relates to how that might translate into commercialization and then one point of differentiation with our program is that the focus on community dwelling patients. So, these are not nursing home patients. And one of the potential benefits of the AXS-05 in Alzheimer’s disease agitation should it be successfully developed is the fact that these patients out of the nursing home.

Great. Thank you.

Our next question comes from Joon Lee with Truist Securities. Please proceed with your question.

Good morning. This is Azam [ph] on for Joon. Congrats on the quarter and thanks for taking the questions. The first question for me is, can you remind us what the powering effect size of the ADVANCE 2 study is? And then, as a follow-up on Auvelity, have you seen some sort of inflection from the increased coverage of $22 million additional new lives on August 1st? Or would you say you're seeing more than an inflection due to the sales force expansion from earlier this year? Thank you.

So ADVANCE 2 is powered very similarly to ADVANCE 1. So it's 90% powered to detect the treatment difference. We have not talked about exactly what the effect size is. But the effect size that its power to detect is similar to the effect size in ADVANCE 1.

And thanks for the question on Auvelity inflection. We are very pleased with the demand that we've driven post the market access expansion. We have seen meaningful growth in both new patient starts and covered claims in addition we've seen a reduction in rejection rates for those covered lives. And so overall we're very pleased with the performance. I think, keep in mind that that win occurs during the summer seasonality months so we expect that to continue to build over time. And so, I don't think it's a fair comparison to say, which created more inflection. But given the fact that the sales force expansion was earlier in the year, it's obviously has more time to make impacts and we've been very pleased with the impact we've seen over the course of the year.

Thank you.

Our next question comes from Myles Minter with William Blair. Please proceed with your question.

Hi, just on a sec on the sales force expansion. I know you’ve still got one large JPO contract that you could potentially execute here. Is that 300 sales force expansion next year incorporating that you get that? Or is that more kind of level of access that you have now? Do you think that that expansion is required and if you bring on another JPO contract, we could get further expansion? And then just secondly, on AXS-14, have you started to engage payers and is that sort of unique benefit on to take that you might say with that agent something that’s honest with them potentially having to cover a branded therapy price? Thanks very much.

Hey, Myles. So, regarding the sales force expansion, it's not specifically tied to a future market access win. It's really to capitalize on the market access we have today in sort of the increase in first and second line access that we’ve experienced this year. But also the growth we've seen in primary care in 2024 are two of the primary reasons why we believe it was the right time to add additional selling efforts. So any additional market access wins would be additive to this expansion and further accelerate performance.

Yeah. And, you ask the question about whether or not you're starting to engage payers as it relates to AXS-14.

Yeah we do talk to payers regarding our pipeline, generally speaking. And obviously, the things that are more near-term to launch are of more interest as it relates to sort of payer or rebate negotiations. That said, I think it's fair to say that payers are very impressed with the breadth of our portfolio. They’ve recognized that these are areas of significant unmet need and although there are existing treatment options, there's still plenty of room to improve on not only symptom improvement, quality of life, but also health resource utilization. And so, we feel very good about the strength of the profiles of 14 and others, And believe we'll have constructive negotiations once we get closer to launch.

In my opinion - this is Mark. To your observation on the peak in particular, we do think that is the important element of our profile.

Makes sense. Thanks for the questions.

Our next question is from Yatin Suneja with Guggenheim Partners. Please proceed with your question.

Hey, good morning. This is Eddie on for Yatin. Thanks for taking my questions and congrats on the quarter. For Auvelity, what sense are you getting from the real world rate of discontinuation, especially as it relates to the pivotal studies and other sort of branded anti-depressants on the market? And then in terms of the coverage, it looks like you're creeping up in terms of the commercial coverage. But what are the major hurdles you're seeing to getting broader coverage access on that commercial channel beyond that sort of 60% to 65% range? Thanks.

Yeah, thanks for the question. Regarding discontinuation, we haven't seen anything significant over the course of this year. And in fact, the persistency that we've observed has been very positive. In fact, one of our internal analyses suggests that although a persistence our pace is that of SSRIs and SNRIs. So we're really pleased with that and there has been no impact from any of the ongoing clinical trials in the marketplace. In terms of hurdles, it's really about aligning on final rebates and utilization management criteria with the outstanding plans. And we are very confident in the negotiations that we’ve had and expect to see access expand and evolve in the near term.

Thanks.

Our next question comes from Ami Fadia with Needham & Co. Please proceed with your question.

Hi, this is Poorna on for Ami. Thank you for taking our question. My first question is, how do you activate the prescription transferability to differ in the fourth quarter with the number of holidays? And could you provide us some additional color on the timing of the data readouts expected in fourth quarter for Alzheimer's disease agitation and migraine? And lastly, does the EMERGE study in any way impact the regulatory decision on Jan 31st? Thank you.

Hey Ami. This is Ari. I'll start with the demand question. So we do expect, there will be some impact from seasonality in Q4. Quantifying that is a little difficult at this time. I would point to Q3, which also there's a seasonality effect and Auvelity outpaced the market. So it's the generic and branded market which both - in both cases. And so, we feel optimistic that we'll be able to continue to grow the brand, but we do expect some seasonality impact in Q4.

Good morning. With respect to cadence of the readouts, I mean, excuse me between now and the end of the year of that that's right around the corner. So I think you can stay tuned for that and we haven't, - we're not this morning, we didn't provide guidance on the exact choreography, but again, it's right around the corner and we're looking forward to providing you updates there. And then, with respect to EMERGE, I think I heard the question is that needed for the – toward the NDA submission or resubmission and we're from a regulatory perspective and so, just as a reminder, that's the, AXS-07 trial that, that will readout and that is not needed for regulatory perspective. Instead, we expect that to whatever we learned from that will inform potential approaching the marketplace and, medical and potential commercial communications.

Got it. Thank you.

Our next question comes from Joel Beatty with Baird. Please proceed with your question.

Thanks. And the first question is for the sales force expansion. How much more reach does that give you? Like, for example, how many more docs does that allow you to cover? And then, the second question is for ADA. When would you expect to be able to file?

Yeah, thanks, Joel for the question. There will be some increase in reach. But I think importantly, there is also a frequency play here more high docile providers. So we feel really good about the markets in which we're expanding capitalizing on the strong market access in those markets. The only thing that will be sort of a dual benefit in getting in front of more doctors. And I have a specific number for you at the moment, but also frequenting those doctors more regularly.

Great. And then as it relates to signing and filing the Alzheimer’s disease agitation, the choreography is that once we have the readouts from the ongoing studies, we will then seek a FDA pre-NDA meeting and then, but in general, the way that we think about it is it takes roughly 6 to 9 months after completing the studies in order to get a package ready for filing.

Thank you.

Our next question comes from Graig Suvannavejh with Mizuho Securities. Please proceed with your question.

Good morning. Congrats on the progress in the quarter and thanks for taking my question. My question is primarily on AXS-05 and AD agitation. Could you please provide your I guess, take on the various potential Phase 3 AD agitation trial outcomes? In other words, I think you said earlier that you feel like hitting on either one of the two would be sufficient to support a filing. But of the two trials, if you are going to only hit on one, how should we think about a positive ADVANCE 2 enabled filing versus an ACCORD 2 enabled SND filing? And then I’ve got a follow-up please. Thank you..

Well, thanks for the question. So just as a reminder, the program consists of newer pivotal studies. And we've already read out two of those studies which are positive So going into these two read outs, there are two possibilities and well, there are several possibilities. But one possibility is that both studies are positive, in other words, ACCORD 2 and ADVANCE 2 or that one of those studies is positive. In either of those situations, that would leave us with three or more positive, efficacy trials to supporting NDA filings and that is more than if needed from a regulatory, statutory perspective. So, if you really good going into these data readouts what we like about the program and the fact that we have four studies is that it would provide a lot of information in terms of product profile and also in terms of the safety profile of the product group in this population.

Okay. Thank you for that. And then, maybe if I could just ask about, the gross to net, I think it was 50% for Auvelity in the third quarter. I might have missed comments around the expectation for the fourth quarter, but any comments just on fourth quarter and perhaps looking into 2025 specifically on the Auvelity gross to net?

Sure, Graig. Hey, it’s Nick. Yeah you're correct with Auvelity GTN in the quarter was approximately 50%. That was a slight improvement from the low to mid 50s in the previous quarters. We would expect it to remain in that approximately 50% range to slightly worsening for the fourth quarter similar to the prior year. And then for 2025, we would anticipate that that similar negative seasonality impact in Q1 that we've seen in this year and then I have to go far an industry see typically and that's due to the reset in the deductibles. And as we would expect that to improve throughout the year similar again to previous years.

Okay, thank you for taking my question

It appears we have time for two more questions. Our first question comes from Ram Selvaraju with H.C. Wainwright. Please proceed with your question.

Hi. this is Eduardo on for Ram. Thanks for taking the question. I had a question regarding the fibromyalgia asset and specifically if you were expecting to hire a discrete sales force to promote sales of that if it were approved? Also if you could give a little color to the binge eating disorder market and the nature of the competitive landscape in that indication?

Yes, so I'll start with the AXS-14 question. The fibromyalgia market is represented by a broad group of prescribers across primary care rheumatology and team specialists. In similar to my comments about 07 the intend market and enter the market in a targeted differentiated way that really leverages the experience we've seen with Auvelity. Right now, I think it's fair to say that there will likely be some of distinct selling, particularly in those specialties where we don't currently call on. But in primary care, which is a large segment of the provider group, there is potential for synergy our existing sales force. And then we'll share additional details as we get a little bit closer to launch.

Yeah, as it relates to, binge eating disorder and the market for that, this is a very large patient population. There is 7 million patients in the US who have binge eating disorder. And there is only one product that is currently approved. And so that’s Vyvanse. So, we think that there is a lot of clinical need and a lot of opportunity to respond to the clinical need with solriamfetol should it be successfully developed.

Great, And if I could add just one last one, if you had any data of background on how Sanofi is doing outside of the US?

Sure, yeah, Sanofi continues to perform well outside the US we do outline the royalty revenue that we receive from Pharmanovia and you'll be able to see that that's been increasing over the last couple quarters as it's been a further prioritized at Pharmanovia in the European countries.

Our last question today comes from Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.

Hey, good morning guys. Thanks for taking the question. Just with the ADA data readout in the near term, what are your current – what’s your current thinking in terms of the launch plans with respect to filing AXS-05 as of Auvelity or as a new brand in the ADA market?

Thanks, Matt, for the question. So, the nice thing about the AXS-05 and Auvelity in the changes is, we do have the ability to file it as an NDA under various forms and there is an SNDA its own freestanding NDA. And their benefits to each approach. We are still exploring the approach that we will take. Stay tuned for that. However, we need to – what we can tell you is that it would be a very well thought out decision.

Great. Thanks, Herriot.

We have reached the end of our question and answer session. And I would now like to turn the floor back over to Herriot Tabuteau for closing comments.

Well, thank you again for joining us in the conference call today. Axsome has built a singular innovative, late-stage, neuroscience portfolio, spanning multiple indications in both psychiatry and neurology, which has the potential to deliver differentiated outcomes for millions of patients and compelling returns to shareholders. We are exposed to keeping you posted on our progress.