Thanks everybody for joining. We're a little late. Logistical issues, but we're good. Marc Goodman, one of the biopharma analysts at Leerink Partners, and we're lucky enough to have Axsome Therapeutics with us. We have Mark Jacobson, who's the COO, and Nick Pizzie, who's the CFO. Thanks, thanks guys for joining us. Why don't we just start with Auvelity and just give us kind of a little bit of a lowdown on what's happening with Auvelity right now, just from a marketing strategy perspective, how you're thinking about things this year relative to what you were doing last year and the year before. Do you know what's changing?
Sure. Yeah. Maybe I'll start.
Yeah.
Thanks for having us, Marc.
Yeah.
Auvelity end of the year, last year, annualizing, just north of $600 million, and it's in its third full year, since launch in 2022. Really pleased with the performance. We've outpacing, some of the peers in the space. Very pleased with that, and that was with, I'll say, a smaller field force. We started with 160, did an expansion in 2024 to 260, and then got to the most recent levels of 300 in 2025. Also with market access, that has evolved and improved over time, and currently we're at 86% coverage. Been pleased with the performance from a revenue perspective and script growth.
One of the things that we are doing in 2026 is expanding the team from 300 reps to 600 reps. Real meaningful expansion, really doubling down on Auvelity, specifically in MDD, but also in ADA, which we have a PDUFA date of April 30th. In preparation for an approval in ADA, we will have a 600 field team detailing Auvelity. Also we do plan to have a small dedicated team, tactical team, specifically around ADA for LTC, for long-term care centers. Auvelity's doing its thing. We're really pleased with it on blockbuster status. Currently, we've shared that peak sales are in that $1 billion-$3 billion range only in MDD, and we've also shared $1.5 billion-$3 billion in ADA.
That, all that aligns with, you know, some of the dynamics and investments and just strategy for the year. It corresponds to what we're seeing, you know, clinically and, you know, which matches the clinical data we've generated in the label, right? Different mechanistically, that different mechanistic profile results in a different clinical profile. It's working rapidly, it's durable, a distinct safety and tolerability profile, then we're seeing that translate into, you know, from the start later line scripts, but it's being pulled up in the treatment paradigm to first and second line account for over 50% of the scripts now. It's gradually increasing quarter over quarter, but first line it's around 15%, and that's ticking up.
You know, so that put it at about 35% for second line. That corresponds to our investment in the sales force for the outlook for this year. About, you know, more than 50% is monotherapy use, and we're seeing more and more uptake in primary care. Latest numbers are about a third of the scripts are coming from primary care, so that's increasing. You know, the trends, it's all tracking very nicely when you zoom out from launch to date, and we expect that to continue, and then we're investing in it to drive it further. Yeah.
the increased sales force will hit primary care a lot more.
Yeah.
Yeah
... I would assume. That also includes, the new indication. You're not changing if you get the new indication approved.
Correct. Yeah. It's complimentary and anticipatory to that.
Yeah.
Not contingent upon...
Right
the new indication. Yeah.
And maybe just the lastly on the expansion. Market access getting to 86% of the total covered lives, you know, we feel that now is the right time to essentially double down to be able to. We know that if a patient gets prescribed Auvelity, that they'll be able to get it through their insurance coverage. Going to the primary care, one of the things that we've been sharing is $600 million, annualized $600 million in revenue. We're only at 0.2% of 1%, so 20 bips of the total antidepressant market right now, and we're annualizing at $620 million. Our goal is to really drive penetration from that perspective.
Yeah. DTC advertising has started?
DTC advertising from a mass media television, if you're defining it that way, yes, we did that in September, and we ran that all through Q4. We had a lot of learnings from our DTC spend. January, February, we're actually off the air. Essentially the way we're thinking about it is with this field force expansion, we are reallocating our resources from DTC to expanding the sales team. We will have DTC, and we're back on the air now in March, and we'll continue to be on the air, but what I can say is we've learned a tremendous amount on what channel between linear and connected TV, and how best to appropriate those funds, and how to actually be more efficient in DTC as well through that, through those four months.
Ultimately, we feel let's expand the field force. We can add DTC back further on, and that will actually complement DTC's ROI by having more boots on the ground. You'll see more pull-through from the DTC campaign.
How much extra gross-to-net did you have to give up as you've really increased this coverage?
Not much. I think we've, if any, I think we've been mindful, as we've negotiated and thought about...
The value of Auvelity, right? We have exclusivity if we have pediatric indication into 2039. We never thought about the short term, we always thought about the long term. From a GTN perspective, we've been, you know, somewhere on average, let's call it around 50% last year. If we think about it, we were in the mid-50s in Q1 and Q2. We were in the high 40s in Q3 and Q4. Overall, roughly 50%. We, as Mark shared, we are, you know, 50% of our scripts right now are either first line or first switch. Not only have we've gotten quantity of coverage and getting to 86% covered lives, importantly, 100% in the government channel, and that comes into play specifically around ADA.
100% of Medicare Part D lives are covered, which is great formulary coverage for those individuals. 78% on the commercial side, so total 86% with good formulary access.
The AD agitation indication, obviously a major focus, very important for everyone to get this. How is that looking? How is it feeling? Have we, you know... Is labeling looking like it's started? Discussions, like where are we?
Sure. I mean, you know, as you know, for a matter of practice for us, we don't comment on play-by-play. If you know, step back, so Breakthrough Therapy designated program, filed and accepted with priority review. PDUFA date is April 30th. Labeling generally, you know, generally begins approximately 30 days ahead of PDUFA. We're outside of that. You know, what we've shared is for us, you know, things are where you would expect them to be at this point in the review. You know, that comment is made based on our, you know, it's a generalized comment, right? It's general, but it's informed by our vantage point of how the review is going.
You know, the other element we've shared is, you know, typically sponsors you interact with the project manager. We haven't seen, you know, within the Psychiatry Division. You know, from our vantage point, things are status quo with respect to the division and its goings on. Yeah, it's coming up and then in a way, you know, Nick's already previewed some of the commentary, the work that is underway in anticipation of, you know, potential FDA action that would allow us then to, you know, launch the program. Excited about that.
The other indication potentially for the drug is smoking cessation.
Yeah
...which probably you don't get a lot of questions about.
Yeah. Yeah.
maybe just give us the quick update on that?
Sure
How fast we can get this indication.
That's always been an area of interest to us just due to the mechanistic, you know, rationale and high overlap with, you know, prior available therapy in terms of, you know. I'm now gonna repeat myself, but the, we think the mechanistic rationale is strong.
Yeah
We've been working on that. The clinical operations set up and getting those gears turning is well underway. That's, you know, we'll be starting that study soon. You know, our expectation is, we'll run a first study that we'll share details on the study design very soon and offer guidance then about timelines. We're excited about getting that program off the ground finally.
Yeah.
You know, we've been really focused on AD agitation, as, you know.
Okay
...all in on that as the next potential program for Auvelity AXS-05. As we work through that, you know, we'll have more to say about other areas such as smoking cessation that we think are really interesting for the mechanism.
Yeah. Yeah. Let's talk some Symbravo. New drug launch. Just give us a sense of what's happening out there. What are you hearing?
Yeah.
How's the product doing?
We, What we're hearing is that the product is doing well, and that it matches the clinical data that we've generated, which is that it's efficacious, it's working well, the efficacy is durable, and that the safety and tolerability profile is, allow, you know, is commensurate or positive for that efficacy profile. Meaning you're seeing patients, try the medicine and then, and then continue to use it.
Where is it being used in the migraine space?
Sure. I mean, initially it's later line, right? The migraine space in particular is heavily managed by payers and for branded entrants. You see that and also just with any new branded product, even in areas of unmet need, they tend to be used later line first because clinicians have kind of their standard of care approach.
Are you post CGRP or you can be?
You can see. I mean, we haven't shared, say, quantitated how many are coming from each line.
Yeah
...or post, pre or post CGRP. You can see utilization in if you're segmenting the market like that, you can see utilization across segments, in both segments.
Yeah
...that makes sense based on the clinical data we generated, right? We've studied the product in patients with inadequate response to prior acute migraine treatment, that includes oral CGRPs, that includes triptans. Then we've also looked at regenerated data in kind of a less inadequate responder patient population. It makes sense how we're seeing it used and we like the early trends. Now to touch on how launch is going, we wanted to have a very discreet tight launch. Sales force, it's approximately 100 reps, that's by design, that's pretty tight, and it's because we wanted to focus on early utilization to see how it performs in a real-world setting in say, headache centers and, you know, with headache specialists.
Those patients, by the way, also tend to be later line. We're understanding the product profile, how it's getting written, how it can be written in, and how our kind of patient support and patient savings infrastructure aligns with that, and then we'll continue to calibrate and refine as we invest further in the brand. We like where it is right now.
We're still in the limited launch phase.
Yeah, absolutely.
Yeah. I think you take a look at what we did with Auvelity with 160 reps in a mass market. We're taking a similar approach with 100 reps or so with Symbravo. you know, ultimately, market access is what our focus is and trying to get coverage. We're roughly around 50% covered lives right now. One of the things that we noted in our most recent earnings is we signed our last contract. Now we have 3 GPO contracts signed to pave a way to be able to get access and have negotiations with those payers...
Mm.
to improve those covered lives.
Got it. Sunosi, what's happening with Sunosi? Anything new? I mean.
A couple.
It's been around a long time.
Yeah.
We're.
Still growing.
We're-
Yeah, very.
...we're very pleased with Sunosi. I mean, it grew 40% year-over-year. You know, we have a very discreet team with that. There's roughly 70 reps for Sunosi.
Yeah.
Very moderate sort of investment as it relates to Sunosi. You know, taking a look, it's a very healthy business. So we're pleased with that, continuing to grow and, you know, with the four indications that we have behind it, that will hopefully further accelerate Sunosi revenue.
Which one of those do you think has the best chance of working?
I mean, we like all the indications. I.
Binge eating.
Mechanistically-
...shift work disorder
Yeah. Yeah.
MDD.
Well-
What's the other one?
Um-
Shift work, binge eating disorder, ADHD.
ADHD. Sorry.
Yeah. Yeah. That small thing. The... Yeah, we tend not to offer, you know, kind of like stacked probability of success for those programs. What's one thing... Shift work, it's adjacent or immediately related-
Yeah
...to the current indication, right? Because of that, actually we previously obtained FDA feedback that we need 1 trial there.
Mm-hmm
...to support label expansion, and that's because the current body of data on label, you know, if the study's positive.
Yeah
...could be considered supportive. That's one way to think about it, whereas the other indications, we're planning two studies. MDD, maybe that's a little more speculative versus ADHD and binge eating disorder, which correspond to impulse control and some of the path, you know, the neuropsychopharmacology around those indications and then the molecule. MDD though, we were excited about, we ran a proof of concept study in MDD and we looked at individuals with... It's kind of a precision approach, individuals with symptoms of excessive daytime sleepiness and those without. We just announced the start of a study in individuals with major depressive disorder with symptoms of excessive daytime sleepiness. That's going on. The other two, binge eating, that study's underway.
We expect top-line results. That's the ENGAGE trial. We expect top-line results in the second half of this year. That would be the first phase 3 trial we're conducting. ADHD, we're starting two studies in pediatrics, one in children, one in adolescents, to complement the study in adults that we have, the phase 3 trial that we've completed in adults, which was positive. There are the... All of it, if you back up, it's coming from, you know, clinicians that, you know, when they talk about how patients do who are prescribed the product for sleep, they talk about its benefits for sleep, but also just global changes that patients experience.
We're, you know, that's, that was the impetus behind doing a full clinical development suite of trials and in a number of indications, and those will... You know, we've had success in some of the initial trials for those already, so we'll keep it moving.
Yeah.
And the-
Positive ADHD.
Yeah
...one, right? One positive phase 3 ADHD-
Yeah
...trial in adults. Now we're doing the Peds and the adolescents. You need 1 for adults, you need 2 for Peds.
Well, we-
2, 3.
Yeah, we're, I mean, we're conducting two of one in each segment for pediatrics, children and adolescents.
adolescents, yeah.
We'll run them in parallel. Those are needed. The FDA has asked, and asks all sponsors that if you're developing a product for ADHD, that you have the pediatric assessments of pediatric clinical trials as part of the initial submission, right? It's dissimilar for other indications where, you know, if you have a pediatric clinical plan, that can often be done as a post-marketing commitment or requirement. Here, it's got to be part of the initial package.
Mm-hmm. What's the hook of your product? How does it fit in? I mean, we have ADHD stimulants that seem to work pretty well, so.
Yeah. I mean, if you look at the adult data, you know, absolute, you know, change in line with the stimulants and a distinct tolerability profile, distinct scheduling profile. you know, you'd wanna be somewhere in terms of highly efficacious stimulant, like efficacy, right? Stimulants are used because they work really well. there are challenges from a tolerability and, say, scheduling perspective. if you're able to show any type of differentiation or complement that available kind of treatment option with a new one, that I think would be pretty exciting. early data so far are more than warrant the additional investment that we're doing, and we're excited about them. We've got these two studies to run and then we'll see.
seeing stimulant like efficacy in a non-stimulant, which is what we saw in the phase 3.
Yeah. Yeah, yeah. That makes sense.
Yeah.
AXS-14, let's move to that one.
Yeah
... talk about reason to believe that the data will work.
Sure
... fibromyalgia market being a good market to go after.
You know, fibromyalgia, it is an underserved market, right? There's only one recent entrant. There were products that are, you know, have been available, but underserved in terms of innovation. AXS-14, you know, as a reminder, we obtained that product from Pfizer. It's esreboxetine, so it's the S enantiomer of reboxetine. Pfizer had run 2 studies, highly positive studies, a phase 2 and a phase 3, in the indication, and then it was shelved for, you know, various reasons on, you know, on Pfizer's part. It was.
We obtained the product, and, you know, we worked on the tech transfer and recapitulating all of the manufacturing and, you know, waiting for all the data there that we would drop back into Module 3. We submitted an NDA, this was last year, and we obtained, we received a Refuse to File. This is the Pain Division. The reason for the Refuse to File was simply that there was an objection to the design or the type of the phase 2 trial, which the phase 2 trial was an eight-week flexible dosing paradigm. The feedback was they wanted a second trial that was analogous to the phase 3, which was 12-week fixed dose. That was the only comment.
You know, the rest of the package was, you know, went through the preliminary filing review assessment. That was the comment that led to the RTF. We feel really good about what we need to do, which is run another trial. We feel really good about the product and its activity on pain, on fatigue, the tolerability profile. We launched the forward phase 3 trial. We did that a few weeks ago. That's gonna be a randomized withdrawal design trial. The reason for that, right, is, we already have 2 positive studies, and, you know, placebo response rates are increasing significantly. We like randomized withdrawal design studies with respect to signal detection.
You know, now it's elbow grease in terms of recruiting and enrolling and conducting the trial. Once that's done, we'll be able to turn around right away and resubmit. We...
Is pain one of the endpoints?
Yes. Yes.
You'll have that on the label?
Yep.
Kinda differentiate.
Yeah. Yeah.
Yeah.
Yeah. I mean, highly statistically significant in the two prior studies. You know, it's clinical development so that's you know, you're always mindful of that. You know, we like the product profile and the data that we've generated. We have high conviction in it and the study design we like. You know, we've got to run the study and.
Yeah
... see what happens.
Talk about the newest product that you just brought in, the one you actually licensed, which is a little unusual.
Sure
... haven't done that in a while.
Yeah.
You've named it 17, so AXS-17.
We did.
So.
17, yeah.
Yeah. What data do we have? Why'd you do it?
It's a subtype-selective GABAA, and we'll develop it for epilepsy. There's a ton of clinical experience actually in generalized anxiety disorder. There's solid anticonvulsant data that we've been looking at that more than substantiates a investment in a clinical program in epilepsy. This really interesting molecule was sitting in, you know, in essentially a defunct structure that had multiple parties involved. It crossed our radar. Why, you know, it crossed our radar, it looked really interesting, and we figured if we could kind of undo the Gordian knot, that we'd move forward with it.
You know, very low risk from a, from a investment perspective, that worked out. Now we've got to do the tech transfer. We're going through an indication selection process right now. 2026 for AXS-17 is all about phase 2 enabling work. You can expect to hear from us updates there and updates on indication selection. Pretty excited. There are, there are lots of different avenues. You know, there's a lot of activity in the space now in epilepsy, which is fantastic for patients. The majority of the epilepsy space is, you know, there are, there are unmet needs. They abound, right? We're, we're going through that now, and we're excited to have updates there.
Yeah, it's new, but so I kind of talked about the economic rationale for why we did it. It also fits very nicely with how our portfolio and pipeline is right now, which is very kind of top-heavy. It's lopsided to, you know, NDA or, you know, late-stage phase three programs. There's a ton of them, but the earlier work, earlier stage programs. You know, we can attend to that, and we'll do that if there are programs that fit in CNS that leverage our internal experience or just-
Yeah, I think our pipeline is really deep for launches into the late 2020s. This is like next gen for, you know, let's say early 2030s.
Yeah.
The GAD data is what the other company was working on?
Correct. Yeah. Yeah, exactly.
you're not gonna pursue GAD. You're thinking-
That's not the plan.
You're thinking epilepsy.
Yeah, no. Yeah, yeah. The data, you know, and, you know, there are pretty robust and extensive models in epilepsy.
Yeah. Well, for sure.
There's the data we have in-hand for the molecule, definitely establishes its anticonvulsant activity, so we're moving forward. GAD, those data are gonna be highly informative, and they'll have utility, especially with respect to the safety and tolerability profile. GAD as an indication, that's for AXS-17, that's not our immediate focus.
Yeah.
What have we not talked about that we should talk about in the last minute?
The
12? Did we talk about 12?
Oh, we didn't talk about 12. I forgot about that one. Please.
The next thing.
One minute of 12.
Yeah, all right. AXS-12, that's NDA stage. We're about to hit the button with the submission that is reboxetine for narcolepsy. We've focused on cataplexy for the clinical program. We're about to submit the Psychiatry Division. It's orphan indication. We'd expect, you know, standard review, we'll have updates as we go and make progress there.
It fits right into our current NOC team, our sleep team. It could be