All right, I think for time we're going to go ahead and get started, but thank you all for joining us in the room and online. I'm Joe Thome, one of the senior biotech analysts here on the team at TD Cowen, and welcome to TD Cowen's 45th Annual Healthcare Conference. It's a pleasure to have with us today the team from Axsome Therapeutics, and joining me for a fireside chat is Mark Jacobson, the COO of Axsome. So Mark, definitely a lot has happened over the past six months and a lot to come during 2025. Maybe if you want to start with just a high-level overview of kind of recent accomplishments and what investors should be looking for this year, and then we'll dive into the specific programs. Sure, and thanks for having us. It's a great conference, and we're happy to be here. So 2024 was a great year for Axsome. We had our second full commercial year for Auvelity. Total sales for the year were just shy of $400 million, and then for Auvelity, about $292 million. So very pleased with commercial performance for the year. And I'll comment, we expect that performance and growth to continue into this year and beyond. On the regulatory side, we got our second, well, just after, just at the start of the year, we got our second internally developed product approved, that's Symbravo for the acute treatment of migraine. Very pleased with that. On the clinical side, we had five trial readouts last year, and a number of those led to the completion of the clinical programs for two of our product candidates. That was AXS-05 and Alzheimer's disease agitation. We reported that right at the end of last year. Then the other clinical program that completed was AXS-12 and narcolepsy. Very pleased with those developments, and that positions us for this year, continued commercial performance, which we're very excited about for Auvelity and Sunosi, the launch of AXS-07, which is coming up, and then essentially three NDA review stage programs, that's AXS-05 and AD agitation. We announced yesterday an update with respect to FDA pre-NDA meeting minutes for Alzheimer's disease agitation. We can talk about that. Then there's AXS-12 and narcolepsy. We expect that submission this year, AXS-14 and fibromyalgia. When we reported year-end, we had commented that that's in the filing phase of the NDA submission. That's fantastic. And then we have a number of clinical trial readouts coming up, and two of which are coming up this quarter, and both for solriamfetol, or Sunosi. So just an incredibly busy year where we expect to continue the momentum from last year, and team's excited, heads down working. And so I think you'll be hearing and seeing a lot from us this year. Great. And maybe we'll start with Alzheimer's agitation just because of the update this week. Obviously, we saw the data end of last year. You have three positive pivotal studies, one that was directionally positive but didn't quite hit. You released earlier this week some feedback from the pre-NDA meeting. Do you want to just touch on that and kind of your confidence that you have a reviewable package? Sure. Yeah, so we're very pleased with the package we have, and the pre-NDA meeting is designed to, and the intent of that is to align and agree with the FDA on the content and format of the submission, so what we shared this week is that we have the formal meeting minutes where we have alignment on the clinical and non-clinical package that we'll be presenting to facilitate their review of the risk-benefit profile. We shared that we will be submitting that as an sNDA, so this will be under Auvelity, so an efficacy supplement for the Auvelity NDA, and we shared that we expect to make that submission in the third quarter, so team's on it, and we're pretty excited about that, and yeah, so I think we'll have a number of updates on the progress there in the months ahead. Perfect. And you do have a breakthrough therapy designation for the indication. So when would you expect a launch here? And you did highlight that it's an sNDA versus an NDA. I guess, are there any differences there? Why one versus the other? So it does have breakthrough therapy designation. So we've received breakthrough therapy designation in the indication. That means it is eligible for priority review. The FDA makes that determination at the time of submission. But where we are now is it's eligible for priority review, which is great and we're pleased with. And ultimately, because it's an efficacy supplement, the timeline and the associated PDUFA date, FDA would tell us that upon submission, but it's a couple of months different here or there. So that would third quarter submission, if you do the math, that's a potential Agency decision early in the coming year. So we can crystallize that information, I think, later this year. And in terms of the package, it really doesn't change. There are some technical aspects, but the clinical package is the same in sNDA or NDA, which, again, we're very pleased with three positive trials, different trial types, and so a very consistent efficacy and tolerability profile. So we're very pleased with that, and in cases of interest, what's different is you're amending, you're supplementing an approved NDA versus for certain sections referencing the approved NDA, but the meat of it, the content is the same. Perfect. And maybe can you talk a little bit about the company's expectations for how large this indication can be for Auvelity? Is everyone a candidate for chronic treatment? Can you kind of walk us through the opportunity? Sure. There are about seven million, I think it's like 6.8 million individuals with Alzheimer's disease in the U.S., and up to 70% have, approximately 70% have agitation. So there are a lot. There's only one approved product right now, and the majority of the primary way patients are treated is with off-label products, antipsychotics, things like that. The product that is approved is an antipsychotic. So AXS-05, an entirely different mechanism from what's available right now. And so we're excited that should the product be approved, we can offer something that's distinct and a new type of treatment for patients mechanistically. Perfect. And can you talk a little bit about how Alzheimer's agitation will fold into your existing sales force efforts with Auvelity and maybe what sort of amplifications or changes you might need to add in? Yeah. So the Auvelity Field Force as of this quarter is now about 300, especially the account managers, so the sales reps. And there is potential overlap right now from a target perspective, but we would anticipate probably some type of additional expansion in line with potential approval. Exactly what that would look like, I think it's a little premature to say, and that we would share that, say, upon or around a potential action date. But definitely, we see a ton of opportunity there that is distinct from the current opportunity that we're working on with depression. And then there's also there are areas of overlap that make a lot of sense that we can leverage the existing sales team and infrastructure for additional potential label expansion and potential synergy. Perfect. And obviously, in neuropsychiatry, you often have good drugs that sometimes just don't work in a trial. Do you have any thoughts about why maybe the ADVANCE-2 study didn't end up being positive in statistical significance? What we know is the complete clinical package with the three positive trials, the long-term data that we have, and then, say, the open label data. It's all very consistent, including ADVANCE-2. When we announced the trial results at the end of the year, Dr. Jeffrey Cummings joined the call. And he had some commentary that in addition to high placebo response rates in psychiatry, in this patient population in particular, you also see what he calls trial response, right? So So wherein patients are seen by a clinician or a healthcare provider much more frequently than they are, and that additional care is beneficial. And so he had that observation. And the team, of course, those data go into the NDA, and of course, those were part of the meeting package that was shared with the FDA for the pre-NDA meeting minutes that we received. So it's all there, but I think those are two potential reasons. Maybe jumping over to current Auvelity in MDD, I guess, what are you seeing in terms of uptake? Where in the treatment paradigm is Auvelity being used? And are you seeing changes now versus when you launch the drug? And do you see future changes coming? Sure. Yeah, no, the uptake is we're pleased with it. What we saw last year and current trends and our expectations are that uptake will continue. And where we're seeing it right now is about 50% is coming first or second-line use, which is great because then it is a different treatment option, and we're seeing good persistence and compliance, and just the feedback from clinicians is very positive. So what we're doing there to drive continued growth is obviously the market is very large, so there's still opportunity from that perspective. But if you think about strategy tactics for continued growth, I mentioned we expanded the field force again this quarter. We added about 40 additional reps, and they're in the field now. So we'd expect to start to see impact, say, over the next one to two quarters. Another thing that we'll be doing this year is a more robust DTC effort. We have been doing DTC, excuse me, but it's mostly been online, targeted online efforts, which is the norm now. We think this year the time is probably right to go broader with a disciplined DTC linear TV effort. We'll be doing that. Then we continue to expect to drive additional covered lives in the commercial channel and improvements in the quality of coverage that's in place. We expect it's still in growth phase, and we expect that to continue. And on that latter point, can you talk a little bit about ease of reimbursement as it stands right now? Are there prior auths that people are encountering, or how easy is it to get the drug when you want to? Sure. It depends on the plan, right? And so you can look at, you can see, right, about 50% first or second line. And so that's a good reflection of the Auvelity availability for patients to get on and for doctors to prescribe it across a variety of patient profiles. And so we expect that to continue. But if you step back and look at the class and how payers manage the class, it does vary, right? So there are some, it tends to be the platforms of the payers and the GPOs for if they prefer to manage through steps or through prior auths and fewer steps. So we'd expect coverage to be steady state coverage, to be in line with what you see for the class. And then there are mixes, but we like the mix currently and expect that to continue to improve. Perfect. And earlier this year, you announced a settlement regarding the potential entry of Auvelity generics. Can you maybe touch a little bit on that? Why was now the right time to settle and kind of what are the terms there? Sure. So that was a settlement with Teva, the only first filer for a generic for Auvelity. And so we settled entry date of March 2039. That's with pediatric exclusivity. Or if pediatric exclusivity is not obtained, it would be September 2038. So that gives us 14, 15 years of operating time or on market time. So that's fantastic. And why now? I mean, that's just in virtue of the discussions between the two parties. So I don't think I have anything especially interesting or enlightening there, but it happened and it's great. And because there was only one first filer, we're done. So it's a really great place to be this early in launch. Perfect. And you recently did get the approval of Symbravo for migraine and then also released some interesting data post-CGRP with the drug. I guess, where do you expect this drug to kind of slot into the treatment paradigm? And can you remind us on launch timing and plans? Sure. So it was approved earlier this year. And then when we reported year-end results a few weeks ago, we had shared that we expect the product to be commercially available in about four months. So that's still tracking. And where it will be used, it's interesting. The data that we've generated is very robust and distinct from what you typically see for migraine registration trial data or complementary data. And so we have data in typical patient profiles, but then also in patients that are inadequate responders or non-responders to prior oral acute migraine treatments. And that's great because we have it in a variety of types of patients, right, and just kind of all comers with prior migraine treatment, non-response, and then in particular, inadequate response to oral CGRP. So the data for clinicians and payers to understand the value profile of the product from an efficacy perspective and tolerability perspective, it's very, very robust. And then if you talk to clinicians, right, so Stewart Tepper, one of the key KOLs in the space, his perspective is that you could use it in a variety of patient profiles, including early in someone's treatment journey, and that just consideration will be market access considerations. And so that's one thing the team is on right now and working on in anticipation of launch. So we feel good about the confluence of those things, the efficacy and tolerability data that we have, but then also the commercial operational activities that are underway to facilitate clinicians being able to use the product in the settings that they think it's appropriate for. Do you currently have the infrastructure to market and sell this right now, or do you have to do any sort of changes? The infrastructure is there. What is being built out right now is the sales representative team. So the sales leadership, they have been hired, and the training and marketing materials and things like that, that's all underway and facilitates the launch date that we mentioned. The primary next thing is just hiring of the sales representative team, which is underway as we speak. Perfect. And maybe jumping over to some of the phase 3 readouts that are expected this quarter. Obviously, you have a lot of experience in MDD through Auvelity. You're studying solriamfetol in MDD. Can you kind of give us some background? What have you seen either internally or through where this drug came from previously that gave you the confidence to study in MDD? Sure. In MDD, so that's the PARADIGM, phase three trial. That's reading out this quarter. The genesis of that is information on mechanism of action, mechanism of disease, and in particular for depression, KOL feedback and KOL experience prescribing the product. It's approved for excessive daytime sleepiness, but the one thing they note is patients do better from an excessive daytime sleepiness perspective, but they also experience global changes. So it's that feedback that led us to be interested in MDD. I mean, we're interested in a number of indications too, and we're really excited about solriamfetol and Sunosi in general. But then when you look at our expertise, our clinical trial design and operational expertise, we have deep expertise in major depressive disorder and conducting trials in an efficient, timely, and cost-effective manner. That for us, it's very much worth exploring and conducting a study in depression. I mean, I think you're alluding to that it is somewhat speculative. That's totally true, but we'll feel good about the answer. We can conduct quality trials in depression. That's what we're doing. We'll have an answer soon. Then we'll see. Then if there's a signal, we'll continue the development. We'll know very, very, very soon because it is on track for this quarter. When you think about success here, is it just hitting stats on the MADRS, or you mentioned maybe it might work better in some patients that have different sleep quality? Are there other measures that you're going to be looking at to kind of? Yeah, I think success here is conducting a quality study and if we see a signal, and in particular, we are looking at, given the product profile, we are looking at patients with depression with and without excessive daytime sleepiness, so I think if we see a signal, that will be excited about it, and then that would inform the continued clinical development in the indication, but we'll see, but you're correct. We are interested in, again, given the product profile, the mechanism of action, the potential overlap with sleep. There is a titration period in this study. Can you kind of walk through why it's incorporated here? Sometimes there is a titration with Sunosi, sometimes there's not. Can you kind of? Yeah, it's just to match the label. And what's approved now is 75 mg and 150 mg. There was historically additional work at higher doses, and so we're looking at that too, just from a dose response perspective. And so you titrate up. So we'll see. And that's another element of if we do see a signal, finalizing what the titration algorithm and maintenance dose would be. So we'll see. And then maybe moving on to ADHD, also expecting the phase three trials from that this quarter. Maybe can you touch on the phase two results that kind of led to studying it here and maybe help you get this opportunity? This feels like maybe it could be one of the larger disconnects between the stock trading and opportunity in the pipeline. Yeah, definitely. So we started the program. So this is the FOCUS phase 3 trial also reading out this quarter. And we started the study again based on KOL feedback and insights and mechanism of action, mechanism of disease, and what we just know about the product, the product candidate itself. We started the study then. There was an ongoing investigator-initiated trial. This is by Dr. Surman at MGH. And that study did read out. That was a phase 2 positive trial, which is great. We don't find that disagreeable, but it wasn't an Axsome study. But I think that contributes to the data that exist with respect to the rationale for exploring and running the trial. So we'll see soon. And yeah, I think it is. We know folks are doing their work now around the trial, which is great. But we'll be able to really talk tangibly about it also very soon. But we'll see. Can you talk about the unmet need in ADHD? What proportion of patients really aren't served by either stimulant or non-stimulant options? It's a very large patient population and underserved, right? So there are stimulants, non-stimulants, and there seems to be high patient dissatisfaction with finding the appropriate balance of efficacy and meaningful efficacy for the bulk of patients balanced with tolerability, right? And so right now, there is a range of high efficacy and tolerability considerations versus improved tolerability, but differential efficacy. So we'll see where if we do net out in that kind of range. But we already know things about the product that are really compelling, right? We know the scheduling, we know the tolerability profile, we know things about its activity and sleep. There were data that we reported about a year ago in cognition and potential benefit to cognition. Already we know a fair amount about the product profile that if it does work in the indication, that would position it as potentially being able to deliver on some of the areas of unmet need for patients with ADHD. It seems like the company will need one positive study in adults, one positive study in pediatric patients. Can you touch on the progress of initiating and starting the pediatric study and kind of how that ended up maybe being tied to the adult readout? Sure. So we do need an adult study and a pediatric study for the initial submission and the prep work, the regulatory prep work, the protocol design, and the entire pediatric investigational plan. That work is underway, and the team has been working on it in the background. And it so happens that it is lining up to come serially or after the adult trial. But the work is underway. And so if we see a signal, we'll be ready for next steps in the program. But we do need one in each for the initial submission, which is obviously distinct from most other indications in psychiatry where you can start with the adult studies and then as a post-marketing requirement, follow up with the pediatric investigational plan if appropriate. So here you need it from the get-go. When you look at the field in general, if you do work in adults, do you tend to also work in pediatric patients? Do you think the adult study, if it's positive, is pretty de-risking when you think about moving into peds? Oh, I mean, I don't know if there's an additional, I mean, some of the trial paradigms are a little bit different, but I don't know if there's additional distinct risk from a mechanism of action or disease perspective. Obviously, you have to get the dosing right and the PK associated with that. But I think probably when you think about psychiatry, probably the larger risks are still in place, which is expectation bias, right? And so each positive study you have that substantially drives expectation bias for a subsequent trial. So I think that maybe that would be, at least in my mind, maybe the team would differ, but that would maybe be a larger "risk" than just in a pediatric profile. And then maybe can you touch a little bit about AXS-12, kind of where the company stands in terms of submitting that filing? You do obviously have Sunosi with excessive daytime sleepiness with narcolepsy. How is this going to fold into your current efforts there? Sure. AXS-12, the action items are in NDA submission this year. Our guidance is that next step is a pre-NDA meeting with the FDA. So stay tuned for that. And that's tracking. And then should the product be approved, how does that work from a commercial infrastructure perspective? You're right, we have Sunosi. And so we have a sales representative team that is focused on sleep right now. So that is obviously highly relevant to potential approval and targeting effort with AXS-12 should that be approved. And so very deep synergies from a commercial infrastructure and team perspective wherein we think that could be, again, if the product is approved, a very efficient potential launch. And then, can you remind us lastly on the sort of near-term regulatory submissions, AXS-14, you didn't have to run any additional clinical work since you got the drug from Pfizer, I guess. What's your confidence that you have enough for review here and kind of what's the status of the submission for AXS-14? The update that we had provided at year-end was that it's in the publication phase, and so we like that and where we are. I think next updates are potential FDA acceptance, and then we'd expect that to be a standard review. You're right. The clinical trials were done. We did have to recapitulate the manufacturing, and so just as a reminder, this product we obtained through an agreement with Pfizer. We're excited by fibromyalgia. It's a very large area of unmet need, right? There are only three products approved, and there hasn't been any innovation in the space for, I think, 10, 15 years. There's a dramatic patient need. It's about 17 million patients. The available therapy right now does not address a lot of the key and some of the primary considerations for patients. One of those is fatigue. In the clinical trials that were conducted, we see an important impact on fatigue and how patients with fatigue do with AXS-14, so yeah, that's not too far away, so we'll know, and then I think if should the product be approved, we'd be able to talk about where that may fit in the treatment paradigm and then how we plan to detail it. You indicated you brought that in, and then obviously with Sunosi was a good bit of BD, and you ended up selling the rights for more than I think you paid for the whole drug. How does the company think about additional BD efforts? Obviously, you have a lot going on internally, but what would interest you or how are you thinking about that? We have a lot going on and a lot going on the commercial side in terms of launches, additional launches, and then a regulatory side. So potential additional launches in the not-too-distant future. So there's a ton of work, and then there are numerous phase 3 stage programs. So we're very pleased with the amount of work we have right now in the state of the pipeline. But you mentioned Sunosi. Should there be something that fits from a bandwidth perspective wherein we see value for patients? And if we see that we can make sound business decisions around something and return value to shareholders, that's something that we would consider. But there's nothing we have to do there. So we are being very mindful of ensuring bandwidth and focus remains on the commercial activities and regulatory activities, etc. So we'll see. So we're in a nice position of not having to do anything but having operational flexibility if there's something that fits. Perfect. Awesome. With that, we're out of time. So thank you very much for joining us. Thanks for having us.