We're going to get started with our next session. I'm Andrew Tsai, senior biotech analyst at Jefferies. Thanks for joining me today. It's my pleasure to have the Axsome team with me. To my direct left, Mark Jacobson, COO, and to his left, Nick Pizzie, CFO. Welcome, both of you. Thanks, Andrew. Thanks for having us. Great. As usual, would you mind providing a brief overview of Axsome, all the programs you're working on? Congratulations on a recent approval, by the way. It'd be helpful to briefly talk about the programs, and then milestones over the next six to 12 months would be very helpful. Sure, happy to do that. Axsome is a CNS-focused biopharma. We have three commercial products approved for four different indications. That is Auvelity, which is approved for major depressive disorder and, most recently, Alzheimer's disease agitation. We're very excited about that. We'll touch on that. There is Sunosi, which is approved for excessive daytime sleepiness in narcolepsy or obstructive sleep apnea. Our third product is SYMBRAVO for the acute treatment of migraine in adults. The pipeline behind that is very deep and broad. There are six product candidates that we are developing across 10 different indications that span different programs in psychiatry and neurology. I'll try and do this very quickly. The first and foremost on the commercial side, the milestones and activities between now and the rest of the year, the launch of Auvelity in Alzheimer's disease agitation, that is on track for this month. We can get into that. We're very excited about that. Then the balance of the year is really commercial performance and educating potential prescribers. Again, we'll get into that. We're very excited based on the state of affairs for Auvelity to date and launch to date in major depressive disorder, continued growth there, and then growth in Alzheimer's disease agitation. Same for Sunosi and Symbravo. Turning towards the development pipeline. With Auvelity, the development code for that is AXS-05. We think the product and product candidate, it targets NMDA and Sigma-1, and we think that's very interesting in a number of other neuropsychiatric indications. We are starting with smoking cessation, so we'll be starting a study in that indication soon. We said that would be for the second quarter. We're interested in other areas, too, and we'll share more about that as the year progresses. We have the name of Sunosi, or solriamfetol is the product name or the molecule. We have four different indications that we're working on there that are all in active phase III development. We have ADHD, so we have a positive study in adults that's been completed, and the action item for this year is to launch the two phase III trials, one in each children and adolescents. That is on track for this quarter, so stay tuned. It's enrolling that program, and once those are done, if those read out positively, then we'll be filing a package there. There's major depressive disorder in individuals, patients with symptoms of excessive sleepiness. That's a precision approach to MDD, and that study is underway, so we'll continue enrolling there. There is shift work disorder. That study is underway. Top line next year. Finally, for this year, there's the binge eating disorder phase III trial, which we expect top line results later this year. That's solriamfetol. We have AXS-12. That is our product candidate for narcolepsy, in particular cataplexy and narcolepsy. We've submitted an NDA to the FDA for that program. Next step there for this year is to announce the FDA's acceptance decision. AXS-14, we're conducting a phase III trial on that program. For this year, it's continued enrollment and driving enrollment there. We already have two positive, highly stat sig trials for that indication, so we're excited about that study. We have two new product candidates, AXS-17 for epilepsy and AXS-20 for schizophrenia. The work this year for those, it's trial-enabling work and tech transfer. Great We'll pause so we can actually get into some questions here. Thanks. Thank you. I appreciate it. I'd like to start with Auvelity, of course. You recently raised the peak sales guidance, currently approved in depression and Alzheimer's disease agitation now. You raised the peak sales guidance to $8 billion, and you've mentioned that does account for IRA impacts potential. For Auvelity, when could IRA impacts start to happen, and when do they get implemented? Are you- Yeah, it would be 2031 or 2032. Great. Are you saying that you can grow through the IRA to get to $8 billion, or are you hitting $8 billion before IRA happens? We haven't given specific guidance on when we'd actually hit the $8 billion, but we've taken into consideration any type of IRA negotiations into that $8 billion. If you're going to be doing $8 billion a year, you're raking in a lot of cash. What do you do with that cash? It's a good problem to have, Andrew. Thank you. I think the main focus on how we are deploying capital right now is heavily focused on just increasing growth top line for our revenue. Coming out of the gate right now, we've already expanded our team for Auvelity from somewhere in the neighborhood of 300 to 630. Our focus right now from a capital deployment is top line growth, and we feel like our best ROI is with our sales reps. Okay. Right. For now. Yep. Then maybe just starting actually with MDD, some housekeeping questions, guided to do $4 billion, give or take, just for this indication alone. When I think about precedents of depression drugs, I guess Spravato, Vraylar, Caplyta, why do you think you can do more than those drugs in peak sales? The data are just based on the current trends and uptake that we're seeing and how we're investing in the product. Already the run rate is about $600 million. We prefer not to tether too closely to other brands in terms of how we assess our own performance. Given the question, if you look where the brand is currently pacing, it's doing very well with respect to some of the other programs in terms of attaining our guidance. We'll just share that, but it's really just uptake and where we are now with weekly scripts, persistence and compliance, access coming online to an even fuller extent, number of covered lives, we can get into that, and continued evolution in the quality of coverage that's in place. Look, if you're going through the exercise, if you go back to the early aughts and look at other branded agents for MDD, in Auvelity, it's for MDD. It's not adjunctive. If you were to bring those into today's current dollars and pricing frameworks, it's in line with those. Yeah. The market has grown since then. There are all different ways to look at it, and it's all consistent. Right? You want to talk about penetration- Sure. Yeah. Just total, yeah. Yeah. Thanks, Mark. What we've been able to do with a very minimal investment compared to our peers is pretty significant, and that's why we're looking to double down now even further on our field force. If you think about us annualizing three years in to north of $600 million with, on average, we probably had 225 reps. I think that's a small fraction compared to our peers. With minimal, if any, direct consumer advertising, meaning mass media, TV spend, and improving market access, originally coming out of the gate with very mediocre market access as a new entry to the space, but improving that to where it's at today, and that's more recently the second half of last year, we're at 86% covered lives, 56% first line or first switch is meaningful. We're seeing the growth in market penetration. We were, as of the end of Q1, roughly 22 bps, only 22 bps of the entire antidepressant market. That is an increase by, I think, north of 50% from where we were in Q1 of 2025. That is with the team that we originally had prior to the expansion. You take a look at the NBRx, which is our leading indicator, and that is roughly 50% higher. That's around 30 to 32 bps of what our market share is. That'll be a nice leading indicator. I think one thing that goes unnoticed here as well for additional growth driver is while we did receive the approval in ADA, this actually unlocks a major subpopulation for depression in long-term care facilities. We have not historically called on long-term care for any perception that we were detailing off-label, so we kept that completely out of our target list. This opens up that subpopulation where there is a significant prevalence of depression in LTC, so that's going to be yet a further driver for MDD as we further expand the team. Very helpful. Gross to net, I think it's been in the high 40s, mid-50s range right now. Within depression alone, is there more room for improvement on net price, or are we there, basically? No. It's actually a good carry forward from my last response. As we are now entering in LTC, we may see more patients with depression that are on Medicare coverage versus commercial coverage, which because there's no copay specifically around in Medicare, that net price could be more favorable than what we've seen. We started out of the gate in Q1 in the low 50s. That was an improvement from the year before, where we were in the mid-50s. We would anticipate a similar trajectory in 2026 versus 2025. As a reminder, we ended Q4 2025 in the upper 40s. I think we're pleased with where we are from a net price perspective, where we are from a total lives covered, as well as, importantly, the formulary coverage. Great. Shifting to Alzheimer's agitation, sounds like you're about to launch. Are we on track for this month? Yep, we are on track. The steps to launching, the product is of course already available. What we are doing is ensuring and completing our training process, and launch is really the initiation of detailing and educational efforts from the sales team, obviously the deployment, so to speak, of marketing materials, and that is on track. Great. Let's just say you launch June. I guess the next update would be your Q2 EPS in August. During that time, what kind of metrics are you considering sharing with The Street? That is something that we are going to monitor to see what's helpful to share. If you back up, when we report, we plan to report just total Auvelity numbers. We will look to be helpful for folks to show and speak to how the product is growing uptake. Historically we've shared information about number of prescribers, number of unique patients, and obviously coverage. That will continue to evolve over time. It will be in line with that, but exactly what we'll share is to be determined, and obviously it's a new indication, and then we're also going, as Nick mentioned, into long-term care. We'll seek to be helpful. KPIs in particular that we plan to share. Okay. Bigger picture, fundamentally, there's you, there's REXULTI, and that's it. Remind us why you think you're a superior product to REXULTI, why you think you can get way more traction. That'd be helpful. Sure. There's us and REXULTI as approved agents, right? There are over 20 million scripts written and well over 95% today are off label. On label, it's REXULTI and now Auvelity. I'll just talk about Auvelity and its label and why we're excited about it. If you step back, the need is there, right? We talked about the number of off-label scripts, but the Auvelity, we have data from different types of trials showing different types of efficacy. A rapid separation versus placebo, starting at week 2 and continuing thereon. That's coming from the parallel group trial that we ran. On label, we also have a randomized withdrawal design study, which shows long-term durable efficacy, which is great. That's unique to Auvelity, is that type of onset of action, so to speak, and then duration of treatment effect. In fact, what's in the label and what we saw clinically is that if you take patients off the drug, they have a much higher rate of relapsing than if they stay on the product. That's very compelling and that's specific to Auvelity. We have the safety and tolerability profile, which is also specific to Auvelity, which is very interesting. Both of these, of course, come from the molecule and targets NMDA and Sigma-1. Back to the tolerability profile, there's no box warning for this patient population. We saw a very clean safety profile. The most common adverse reactions were dizziness and dyspepsia. That's it. You don't see classic AEs that you see with the majority of products that are used or have historically been used, say sedation, mortality risk. It's a very clean tolerability profile, especially with the efficacy. We're pretty excited about that in terms of delivering a new option to patients. The need is so large, it's great that there are multiple options available for patients because there are different types of patients, and that's great. Now prescribers have an opportunity to better tailor treatment needs to the patients that they're treating or overseeing. Your sales reps, 630 of them, they will be trying to market Auvelity as the go-to first-line therapy. Is that the strategy? It is. Certainly, if you talk to KOLs, they see a first-line agent. That makes sense to us. Access is in a place where kind of regardless of where it's written, scripts are generally going to be filled. Right. The majority of scripts will be filled. It makes sense, both in the community setting and in long-term care, nursing home, assisted living settings as well. Gross from MDD could improve due to long-term care. How about here for Auvelity and Alzheimer's agitation? Can gross to net improve as well? Sure. We would believe that it would, specifically for ADA, since we think at least 80% of our patients will be in Medicare Part D. We would anticipate a further improvement in GTN there. Okay. Bottom line, you'll launch, it looks like June. Are you expecting the sales trajectory, the uptake to be stronger than REXULTI saw in their initial launch? We haven't guided to that, and part of it is just exactly the early days, there's always volatility, right? The product's already been available for some time. We'll see. We're incredibly excited and the impact in the current NBRx, we expect that to be substantial. Early days, that's always tricky, right? We'll be going into long-term care. It's tricky to tell you exactly how it's going to go, right, in the first weeks and, say, quarters. Overall, we can tell you how, again, that it's going to be a substantial impact. Going into long-term care, that's much different from a community setting where. You're engaging and educating clinicians who see some number of potentially appropriate patients with some regularity on a weekly basis, depending on the type of prescriber. Long-term care, there are different stakeholders that one would engage with and educate. Their decisions tend to be, algorithmic is the wrong phrase, but on a facility basis, decisions for products that are available within that facility tend to be made across a few stakeholders, pharmacy level, director of nursing, and then the prescribers as well. That bringing facilities coming online, so to speak, that can take longer. Okay. The number you're bringing online at any point in time, that makes just telling you how the first few weeks are going to go. Yeah I don't know how helpful that's going to be. Overall, we expect, obviously, due to the adjustment in peak sales, a substantial impact. Yes. Yeah, I think, coming out of the gate, you're going to have the LTCs, which is a completely new segment for us, and there's been work that's already been undertaken. Additionally, we've more than doubled the team. You have a lot of new folks to the Axsome family, and learning the product and getting out there, either building new relationships or reconnecting from existing relationships. It will take some time, but we feel great about early signs, unrelated to ADA. With the expansion, we've seen a nice uptake already in NBRxs. Our NBRxs are up almost 20% over the last couple of weeks, surpassing over 30,000. I think we had 3,200 a couple of weeks ago. We were tracking somewhere in the neighborhood of 2,700 per week. It's just very early stages as it relates to the expansion for Auvelity. We've been pleased with what we've seen. Yeah. Great. If you step back, often conventional wisdom, which isn't always correct, but in our experience, it aligns with conventional wisdom that typically when you see an expansion, you start to see impact, meaningful impact, one to two quarters after the expansion has been complete. That's if you just distill all of. Yeah the specific levers and details we're talking about, we'd expect to see impact in the second half of the year. Last question on this front is, I think what makes Auvelity special, which you've shown in MDD already, is the penetration into the PCP market. First line, second line. Here, Alzheimer's agitation, can you remind us what% of patients are treated by PCPs? Presumably, that would be your marketing strategy on top of long-term care. If you start with first the split in community versus long-term care, the current trends or current script trends are about 60% in a community setting and about 40% in long-term care. In primary care, I think makes up about 35% of the scripts. Primary care, you have psychiatrists and some neurologists. It depends, but you're right. The product right now is being used about, a bit over 50% or half are in monotherapy utilization, and I think it's about 56% or so is first or second line in MDD. You're right, that's increasing because we've gone further out into primary care. We expect those numbers to continue to increase, especially with AD agitation. Yeah, the setup plays nicely going into further into primary care with payer access now established, and specifically around ADA, that 75% will not require PA. Primary care prefers not doing PAs. They're not really necessarily set up to do PAs. Recognizing that a PA will not be necessary to write and to have that script filled is essential. The timing's working out nicely. Okay, great. In the last five minutes, maybe some one-off questions across your program. We'll see how far we get to. Auvelity for smoking cessation, starting phase III, what's the rationale to do this study, and what drives your confidence? When we think about indications of interest, we look for unmet need, substantial unmet need. You have that here. Mechanistic relevance and then supporting data or data that would justify the additional experimentation, and we have all that here for smoking cessation, right? The large unmet need area that's been underserved, mechanistically, there's relevance and then there's good clinical and non-clinical and preclinical evidence for that. We're starting that up. It's a program that we've been kind of chipping away at and thinking about for some time, and now with this approval, ready to get it going, those gears are turning. We'll have more to say about study design and thoughts around potential timelines once we kick off the study. That's coming up. Great. Moving on to another asset, reboxetine, which could be approved, I think March, April. Basically first half 2027 timeframe. Shape of the curve for that drug in narcolepsy type 1, what do you expect? Shape of the curve The launch curve. just launch. Yeah. Yeah. Let's first see if the FDA accepts the submission for review. If they do, if the product is subsequently approved, we're excited about this. It's orphan indication, so it's not ultra orphan, but it's orphan, so you're really talking about thousands of patients. One thing that we really like about that program is it's highly synergistic with the sleep commercial infrastructure and team that is currently in place, detailing Sunosi. The products are also complementary or would be complementary if AXS-12 is approved. Sunosi, that is a wake-promoting agent, and for narcolepsy, it is only approved for excessive daytime sleepiness with AXS-12, that we're pursuing the cataplexy indication. They're complementary in that fashion, and you want to talk about anything for the As you said, it's super synergistic. We already have a sleep team, and putting AXS-12 in the bag of the current infrastructure, really no additional operating expenses aside from maybe some minimal marketing expenses. Revenue falling essentially to the bottom line. Yep. Next is Sunosi for binge eating disorder. There's actually a phase III readout coming up in second half 2026. Bottom line, is the bar for success what Vyvanse, which my understanding is approved, what that shows? Is that the kind of the bar? I think for us, the products are already distinct, and Sunosi is already available. We're looking for a separation in a positive study, and then we would expect to need to run a second study, and then we'll go from there. As you mentioned, there's one product approved. It's highly prevalent, binge eating, and so additional options, we think that's a good thing. Why we say, "Hey, we're looking for a positive study," is the product profile is distinct. Large indication, additional treatment options, so exactly how it fits or potential use case, to be determined. We'll have an answer in the not too distant future. Okay, last question is the same product, going off the shift work data, phase III data set 2027, what drugs should we be looking at as a comparison, and can you file on one phase III? Sure. I think that you can probably guess we tend not to compare ourselves to other programs, other products that are used are modafinil, armodafinil. Again, we'd just be looking for a positive study. Yeah. The agent's wake promoting, and you are correct. In this case, we expect to only need one study, and that's based on feedback from the FDA because the psychiatry division considers it a related indication to the currently approved indications, which therefore can be used as supportive evidence. Right. If we've got a positive study there, then we'll be moving forward expediently with a potential submission. Okay. Well, thanks for all the updates. I appreciate it. Good luck with the launch. Thanks for having us, Andrew. Congratulations. Thanks, everyone. Thank you, Andrew.