Session. Thank you very much to Axsome Therapeutics for being here. We have Mark Jacobson, who's the COO of the company. Mark, I'm going to let you make a quick opening comment, and then we'll jump right into it. Sure. Thanks a lot, Mark, for having us. Really, really appreciate it. It is great to be at the conference. 2025 is already just a great year for Axsome, and that is on the heels of a great 2024 where we had total net revenue of about $386 million, and for Auvelity in particular, about $291-$292 million. Just very pleased with execution on the commercial side of the business for really our second full year of commercial sales for Auvelity. Already, as I mentioned, we started the year very strong. Approval of Symbravo for the acute treatment of migraine. That is now our third product and the second product that Axsome has internally developed. We are very proud of that, and the work is underway to launch that in the coming months, and we can talk about that. The other developments that have already occurred so far this year, the settlement of the patent litigation for Auvelity, and we have a final date now that takes us to March 2039 with pediatric exclusivity, or September 2038 without it. We feel very good about that, and then what that means for the potential for Auvelity and impacting patient lives, and of course then the business impact to Axsome as a result. The other big development so far this year already, we recently announced the pre-NDA meeting minutes with FDA for our program in Alzheimer's disease agitation with AXS-05. We know what we need to do, and we have alignment on the content and format of that submission. It's full steam ahead for a 3Q submission, and that will be via an sNDA. Already this year, a lot has happened, and there's much more to go. I touched on some of those things, the launch of Symbravo, sNDA submission for Auvelity in Alzheimer's disease agitation. This quarter, we've guided for this quarter readouts for solriamfetol in the phase III FOCUS trial in ADHD and the phase III PARADIGM trial in MDD. Those are no change to the guidance there. Beyond that, it'll be continued commercial execution and just execution on the ongoing programs on the clinical side of the house, and also at least one other program that will launch, a clinical program that will launch, which is smoking cessation. Very pleased with the prior year and how this year started and what lies ahead of us for the rest of the year. A lot going on there. Yes. Okay, let's start with Auvelity. Sure. What are kind of the key changes in strategy from a marketing perspective kind of going into this year? Great. So much is just staying the course and the plan, and we're pleased with how launch is going. I would say one update or expansion is simply an additional expansion to the sales representative team. This quarter, we added about 40 additional reps to the team. Now the Auvelity field force is about 300 sales representatives, and those new team members are in the field. They've gone through training, and they are actively in the field now, and we'd expect to start to see impact from, say, from an NBRx and beyond, so flowing into TRx in one to two quarters. That's similar to what we saw last year when we expanded the field force. You have that, and the other, say, expansion of strategy and tactics would be our plans with respect to a broader or larger DTC effort, which we are planning to do later this year. Going on television, streaming across the board. Exactly. I mean, I don't know about across the board, but definitely in what I mean by that is it's not the approach will be it will be TV, linear TV, and kind of other components online, but I didn't mean nightly news, Super Bowl ads, things like that. It will be kind of in our fashion of seeking high ROI and highly rational deployment of. Targeted. Targeted. Very targeted for you. Yeah. What about the marketing message on the DTC? Is this going to be you're going to focus on the new mechanism, you're going to focus on the speed to act? What's the? I mean, that's all coming together right now, but what really resonates is just how patients do when they take the product, in particular that it works quickly, so that it's fast, that the efficacy is durable, so that it lasts, and also that the tolerability profile is distinct from classic AEs that are associated with antidepressants. That really resonates with patients and prescribers. The focus will be on education around those elements of Auvelity. Just remind us how the product is being used in the real world. Yeah. Right now, kind of where things are as of the last quarter is 50% of utilization was in first or second line, and that split, and obviously the rest goes third and beyond, and that split was about 15% first line and 35% second line. We really like that in terms of specifically where we are at this point in launch, and we expect those trends to continue. That has been growing slowly over time, earlier line use. We expect that to continue, and we're pleased with that. Yeah, we'll see how it goes, but I think that speaks to and that ties to just how patients do and clinicians, HCPs, nurse practitioners, they see it, and then that helps them think about other potential appropriate patients and moving it up to earlier line use. Any bumps along the road in the past year or two that you've had to kind of fix and that you can point out and say, "Okay, we've got this. If you heard this story, don't worry about it, we fixed it," kind of thing? Anything? Oh. Nothing major. Nothing major. There are things that are just elbow grease, and I think it's mostly honing in on, to your point, about messaging and how potential prescribers and now patients are educated on the product. Yeah. What about coverage? Update us on coverage and how you're thinking about that. Coverage is about 78% of lives total, so that's essentially everyone, 100% in the government channel and about 63% in the commercial channel. That has been growing over time, and our strategy has been to expand and evolve coverage in a steady and patient fashion while we drive demand and there is additional trial and patients do well and to continue to add covered lives in the commercial channel. That strategy has been the strategy since launch, and it will continue, and we continue to expect additional lives in the commercial channel to be covered. Stay tuned for updates. Yeah. Just remember at the beginning, the strategy was, "Let's show the payers that we can actually, this is a product that matters." Now that you've done that, the negotiating position has been more favorable, and are you looking to sign up the rest? You have one of the big PBMs. I'm trying to remember. Yeah. I think we shared that to two of the GPOs, and that was the last update we provided. Stay tuned for updates to that situation, but it's moving along. I think that also ties to that it's being used earlier in treatment, right? Initially, when whatever new branded product comes to market, you have NDC blocks. New products perplexingly are used in the latest line patients, and depending on how they do, they either kind of stay there or if prescribers see good responses, they'll look for other appropriate potential patients and early in the treatment paradigm. That's what we're seeing. We're seeing that volume and then payers see that. That dynamic is still in place, and of course that corresponds to the additional expansion for the sales team, deployment of a broader DTC effort. What percent right now are primary care doctors that are writing your? It's a good question. I don't have the exact% for you. The majority are still psychiatrists, but part of the recent expansion is the demand in the primary care setting to go wider within primary care positions. We like that, and that also ties to already where we're seeing utilization that makes sense, right? First and second line MDD patients, right? They tend to be first seen. They tend to first see their primary care physician, and depending on where they are geographically, if they're near urban centers or not, they'll either stay in primary care or they may see a psychiatrist. The majority are still psychiatrists. The majority of writers are still psychiatrists, but it's growing in primary care. Last question is gross to net. Just give us a sense of any major changes in gross to net this year versus last year. I mean, we've said that, hey, steady state, we expect to be in line with the class, which is like in the 50s, but ended at about 50%, ended the year at about 50%. What you typically see in Q1 is you typically see that increase a little bit in the class, and we saw that last year for Auvelity specifically. We'd expect. Over the course of the year. Yeah. Yeah. A flattish% versus last year, full year. Yeah. Generally in line and with maybe some evolution in terms of towards steady state. Just as additional covered lives come online, you may see some changes, but we expect to kind of be in the zone that we've been in recently. AD agitation. Everyone's excited about that potential indication. Just talk about what does the FDA kind of say? Where are we here? Sure. I would just say that there was always concerns from the investment community of, do you have enough positive data? Yeah. Yeah. Yeah. Yeah. How do you feel about that? Do you feel better today than you did three months ago? We felt very good three months ago or whenever, I guess it would be three months ago, for when the data ran out. When the trial studies ran out. When the trials, yeah. We felt very good. I mean, three positive studies, that's I think you would always look for a package like that. I think the only reason you would say you'd feel better is you've got feedback, written feedback from the FDA about the plan for the submission and what will be in the submission from a clinical efficacy safety package perspective. Both content and format of the submission. It's always great before a submission, right? Now we have experience getting two products approved with different divisions at the agency. It's very helpful to just have alignment and you let the agency know that the submission is coming and then just get their perspective on the overall package and that included, right, the presentation is the full clinical package. The four placebo-controlled trials, right, three of which were positive, and then the long-term safety database. We ran these extra studies for safety. Now we have the safety. You've checked the box on safety. Oh, we have alignment on the safety package as well. I think the other investor concern was, is a withdrawal study an appropriate study for FDA? Now you have actually two positive withdrawal studies. We have, yeah. I think everybody's like much more confident because you have two, but it's interesting your view is even one would have been good enough. I mean, yeah, don't take our word for it. Just look at what's required from a statutory perspective. It's two adequate and well-controlled trials, and they can be the same trial paradigm or different, right? Actually, there are benefits to having two different trial designs. Yeah. This is going to be an add-on indication to the existing drug. You will market this product as. Auvelity. Auvelity for AD agitation. How do you look at it from the there's one product approved for today? How do you view your marketing hook versus them? Obviously, with only one product approved, there's a dramatic need, patient need, and just for treatment options and approved treatment options, but then also a need is mechanistic differentiation, right? What's approved is a distinct mechanism that there are other products that tend to be used off-label, which are also Auvelity's distinct from those as well, right? It's an NMDA receptor antagonist, and based on the efficacy and tolerability data that we've generated to date, and mechanistically, it's highly differentiated from what's available. We shouldn't expect any added warnings or black box or nothing like that, which Auvelity still has. Yeah. I mean, it's definitely distinct from a class perspective for the warnings that are on atypical antipsychotics. Exactly what the final label will look like, you find that out upon potential approval, right? You have a sense if you enter labeling negotiations. Right now, there's nothing that's on our mind or that is previewed that we would expect to be. Smoking cessation is the next indication. Yes. Just talk about that. I think everybody forgot about that, but. It's always been on our mind, but there's been so much going on that we've been running air traffic control on all the programs and choreographing, say, resource and deployment for AXS-05, and the focus has always the additional development has been AD agitation. That's been the primary focus. Now's the right time to start up the phase II, phase III trial in smoking cessation. That's on track for this year. Is this one pivotal, and you think you'd need two, or? Yeah. That's the expectation is two and that this would be the first of two. We'll see. You'll do one behind the other, or you might even start a second. Yeah. Probably that would be the case sequentially. Just given the resources and the focus. Yeah. It'd be our first study in the indication. There was another study that wasn't conducted by us, so. Yep. Migraine, obviously, the CGRPs have made a lot of noise over the past five or six years. You're getting ready to launch a new product in a few months. Talk about why people are going to use your product, what the hook is. Symbravo, we're pretty excited about it, and it ties to the data we generated and the mechanism of action, right? It's multi-mechanistic, so you're looking to target the migraine cascade in multiple ways to abort the cascade, both of which are very rapid acting, and that's part of the technology. It's based on Axsome technology that we developed. That's the MoSEIC technology where you have a very rapid onset of action for two distinct mechanisms, but then for one of which you maintain a very long treatment effect, and that ties to, again, the technology where you have rapid absorption, but an extended half-life. The data we've generated are in a number of migraine settings or patient profiles, in particular ones that have had inadequate response to prior oral acute therapy. Just in general, inadequate response to acute oral therapy and then in particular, inadequate response to oral CGRP acute therapy. The range of data showing positive treatment outcomes, pain relief, pain freedom, durability, 24-hour pain relief, pain freedom, 48-hour pain relief, pain freedom. It is a very robust data set, and I think that allows us to, now that clinicians have had a lot of time to understand patient profiles and appropriate patients for oral CGRPs and things like that, it is a nice time to be launching. It's like a super triptan. Is that how you? I don't know. I mean, I can see why someone would say that, but in our mind, it's distinct. I mean, you obviously do have a triptan in a highly. The meloxicam's been turbocharged on top of a triptan, right? So you get that. It's not used. Meloxicam, it's an NCE in migraine. What that means is it's meloxicam, it's never used acutely unless it's a hospital setting with IV, but essentially we have a, since you mentioned, essentially we have an oral form of a highly potent NSAID with a very long half-life that has IV-like PK. What's the strategy for sales reps and advertising and put another hundred people in the ground or something? Yeah. We'll say more. Separate sales force. We'll say more about that soon in terms of the numbers, but yes, there will be a distinct sales force. What we have shared is we'll be targeting headache centers. There are about 150 of those in the U.S., and that will be the primary area of focus in the early days of launch. We think that makes a lot of sense. To your point, sizing, we'll share that soon, but it will be in our approach where we leverage our digital-centric commercialization platform. What that is, is that allows us to meet clinicians in the medium or venue that they prefer. That's either a live detail or remote, and the reps have the flexibility to engage across platforms or mediums. Basically, they're more efficient from a reach and frequency perspective. Let's talk about narcolepsy. I want to talk about just Sunosi, which a lot of people are not focused on, but it's actually growing pretty well and just what you're focused on there and anything different from this year versus last year in the narcolepsy. You have a second drug in narcolepsy. Kind of talk about it as one, and then when you have both of them, what's the strategy? The status quo with respect to the current strategy from a commercialization perspective for the on-brand or the approved indications. We have a sales team in place that is Sunosi slash Sleep. Sunosi, it's important to note, is approved for narcolepsy, but just for excessive daytime sleepiness. Excessive daytime sleepiness in narcolepsy and in patients with obstructive sleep apnea. AXS-12, the way we've developed that in the clinical trials that we conducted, which were positive, was looking at cataplexy in narcolepsy. We looked at excessive daytime sleepiness as well and positive separation there too. The field force, next steps with respect to AXS-12, just very quickly, plan to have a pre-NDA meeting with the FDA and then to submit an NDA later this year. If that product were approved, then you can see synergy, but not cannibalization. One plays into the NT1, kind of one plays into everything else. Is that kind of how you think about it? That is how they cohabitate. That's the wrong word, but. Do you think you'll need to increase the size of the Sunosi sales force with that product too? Not necessarily. I mean, so one reason we really like AXS-12, aside from the product profile, is the commercial infrastructure and it's already in place. To add that to the bag is. You're going to get good leverage. Yeah, exactly. Yeah. Good. That product is going to be filed sometime. This year. Yeah. Yeah, this year. We haven't. All the boxes have been checked with respect to data that you need. The clinical work is done. Yeah. We have two studies coming on Sunosi. One is in ADHD, as you mentioned. One is MDD. Let's just talk about the scenarios. ADHD, this is an adult. Let's say the study is positive. What do we do next? If the study's positive, then the next thing is we need to run a study in pediatric adolescent patients. That's required by the FDA as part of an initial submission in adult. A pediatric trial is required. That's the next step. Right. So then you run that study, and then you would get, theoretically, if they both work, a full ADHD label, basically. Kids, an adult. Yes. Correct. That's correct. Yep. In MDD. Talk about that. That is probably a little more nuanced, I suppose. That's more nuanced. In a way, it's more speculative. It's based on KOL feedback and insights and how patients do and just patients that are treated for excessive daytime sleepiness. Of course, they have improvements in sleepiness, but feedback from KOLs is just that there are global changes. We wanted to explore that. In particular, with MDD, we're interested in about half of patients with MDD have excessive daytime sleepiness. We're interested in looking at patients with and without excessive daytime sleepiness. That will be. It has both patients and it's. Correct. Yeah. So it's broadly MDD patients. We get data in both. I mean, you sub. We share. Populations. Yeah. We share that. That is something that we'll be looking at with the study. It's possible that the total study is not stat sig, but one of the subpopulations is stat sig, which is the key one you're looking at, and then we just go after that. Is that kind of what you're saying? Yeah. I mean, we'll know very soon what the data show. I think if we see a signal, then we'd be excited about that. That would determine if we need how many other studies we would need to run. Another drug that probably doesn't get a lot of discussion is fibromyalgia. Talk about the timing of that product and how you see that playing out. That's AXS-12 for, good grief. That is AXS-14. 14. What we shared there, yeah, for fibromyalgia, the clinical data are very interesting. Obviously, impact on pain, that's important. If you look at the need, and it's about 17 million patients, there are a lot of individuals living with fibromyalgia, and pain is, of course, the primary. The data we have with AXS-14 is that there's also a dramatic impact on fatigue, which is really a key symptom or burden of the disease for individuals with fibromyalgia, and there's positive impact there. The product profile is very interesting. What we shared is that that NDA submission, the last update, what we provided when we reported year-end results was it was in publication phase of the submission. The next potential update from us is potential FDA acceptance of the filing, and then standard standards. Who's the audience there? I mean, that potentially is a filing in this year and a launch next year, right? Correct. Who's the audience? What do we do? The commercial team is doing that analysis right now, and there are a number of ways to, there are a number of potential relevant prescribers, and we'll comment on that soon. There has not been active promotion for some time. There will be elbow grease with respect to that, but the targeting process or the analysis, sales ops analysis, that's underway right now. It'll be targeted. This is not, "Hey, let's go to the primary care physicians." More of a targeted approach. I mean, I'm sure it's going to be targeted because that's the way we do things, but definitely these patients with fibromyalgia, they see primary care first, right? Then depending on their clinician, they may be referred to a pain management specialist or a rheumatologist. It can depend, and I think a lot of that may just correspond to the fact that there are not a lot of treatment options. The treatment paradigm as it will be beneficial for prescribers and patients if there's actually something new, and then there's active promotion and education around potential treatment paradigm. All these products we've talked about are all in the United States as far as the opportunity. What's the goals for OUS? The goals for OUS are to partner outside the U.S. That work is underway, of course, for Sunosi. We did that very quickly because there was a very direct and clear path to doing so. For others, there are direct. Auvelity is the key one, right? I mean. Auvelity. Auvelity, now there are multiple pathways, so to speak, in terms of clinical packages that have been completed: AD agitation, major depressive disorder. We haven't commented on specific regulatory body approaches, but the business development plan outside the U.S. is to partner. Maybe I'm just asking this, but is the reason that you haven't partnered it yet because you're waiting for the other indications such that the partner can launch with all the indications at the same time from a timing perspective for IP? Ultimately, what happens with what's launched when, that'll depend. With respect to specifics on business development, we don't comment on them. Your observation that now we have multiple data sets that provides flexibility and allowing, say, calibration for patient needs in certain geographies, we're pleased with that. Good. Okay. Just to finish up, the next thing is the ADHD data and the MDD data, which are both going to occur basically in the next three weeks, right? Yeah. Before the, what's that, Q1? Yeah. Yeah. Okay. All right. Thank you. Thanks for joining us. You're our last stop. Exactly. All right. Thank you. Appreciate you joining us. Good to see you guys. Thanks a lot. All right, man. Thank you. Yeah.