... Okay, guess we'll go ahead and get started with our next fireside chat. My name is Ben Burnett, biotech analyst at Wells Fargo. Pleased to be here with Nick Pizzi, CFO, and Mark Jacobson, COO of Axsome.
Thanks for having us, Ben. Yeah, really appreciate it.
Excellent.
Great conference so far.
Awesome. Well, maybe just to kick things off, maybe can you just kind of give a brief introduction of the company and kinda highlight any near-term catalysts that we should be focused on?
Sure. So Axsome, CNS-focused biopharma. We have a broad portfolio of three approved products, and we can discuss that, two of which we developed internally, Auvelity for major depressive disorder and Simbrivo for the acute treatment of migraine, and then there's Sunosi for excessive daytime sleepiness associated with obstructive sleep apnea and narcolepsy. So those are the commercial programs, and we're in growth phase for all of those. We have a very robust development pipeline behind those, a number of indications in terms of potential expansion for the approved products, so Alzheimer's disease agitation, smoking cessation, ADHD, binge eating disorder, shift work disorder, as well as a number of other programs that are NDA stage. That takes us AXS-12 for narcolepsy, and then earlier stage programs that we're moving along.
It's a great time for the company. The fundamentals for the company have never been better, and you know, we're happy to dig into the details here, but thanks for having us, and I don't know if you want to comment on-
Yeah, sure. Maybe a little bit on the, on the financials. So, Q2, we hit a milestone of $150 million, for the first time in net sales, $120 million coming from Auvelity, so on track for $500 million in annualized sales. $30 million for Sunosi, which we acquired from Jazz Pharmaceuticals a couple years ago. And then finally, as Mark mentioned, we launched Simbrivo, just for about two and a half weeks in the quarter, and we recognized about $400,000 in the quarter. Balance sheet very strong, north of $300 million in cash. That takes us to cash flow positivity. So just a little bit about the-
Okay.
About the financials.
Great. A ton to dive into, but maybe we can start with AD, Alzheimer's disease agitation. So AXS-05, kind of the generic name, Auvelity. I guess question number one, are you still on track, do you believe, to file an sNDA in the third quarter?
Yes. Yes, we are.
Okay.
Yep.
That was easy.
Yes. Yeah.
Maybe you could also talk about the kind of commercial opportunity in AD agitation and kind of frame for us... You know, there's a drug, Rexulti, that was approved there. There are some drugs that are maybe used off-label, but maybe frame for us kind of what the unmet need is there and kind of what that means in terms of the commercial opportunity?
Sure. Substantial unmet need, right? There's as of recent now only one product approved, and so large need, what we've guided to. You wanna comment on potential peak sales?
Yeah, sure. So for ADA, we see potential peak sales of $1.5-$3 billion. So there is really one product out there in Rexulti. It's atypical antipsychotic with a black box warning. And it's laying the groundwork, which is great for a truly unmet need. It is an atypical. It does have a black box warning, you know, and you know, if approved for Auvelity in ADA, we believe the efficacy and the safety profile is a true differentiator for patients.
Okay. It's a good point. So the key differences are, at least between the Auvelity label currently, and I think maybe you could talk about your expectations if that were to be approved in ADA, but Rexulti has a black box label. So is it fair to look at kind of the launch cadence of Rexulti in agitation, and is that something that should guide us?
It's the only case study or analog that's available, so it's informative, and definitely there's work being done. The commercial dynamics are interesting, right? Because the product. Atypical antipsychotics are used currently off-label, and now, in the case of Rexulti, on-label in the indication. So that, maybe the approach there would be a little bit different for Auvelity, should it be approved in the indication, right? We're not looking to convert off-label utilization, so to speak, right? It would be either, you know, frontline or, in certain cases, I guess, you would potentially be seeing some switches, but really, it would, the expectation is that'd be a frontline branded product. So it would be a different commercialization approach.
But yeah, I think it's informative. The market's being educated in terms of, you know, potential patient profiles and potential appropriate patients for different types of potential therapy, which is great. And so it is good that there is now at least, now that there's one labeled product, and then, you know, we're barreling towards a potential review and then a potential launch.
Okay.
Yep.
Okay.
Just maybe just on Rexulti specifically, if you take a look at Rexulti scripts, I think they're growing in totality in the high single digits, maybe low double digits. The vast majority, if you actually start double-clicking down on by channel where those scripts are written, you really see the robustness in the Medicare channel of it being somewhere in the neighborhood, I think, quarter over quarter, year over year. I'm sorry, Q2 versus Q2 of last year, was north of 40%. The majority of that growth is coming in that Medicare channel, which presumably is the ADA indication.
Oh, super interesting.
Yep.
Okay.
And then just with regards to the package, so I think, you know, you've conveyed that there's a number of positive studies that you have under your belt with this drug in AD agitation, including two randomized withdrawal studies. I think, you know, we can look at Soleno and see sort of a positive example of sort of what the FDA's view there is. Understanding that this is a sensitive situation 'cause you're in dialogue with the FDA, but what can you share about the FDA feedback with regards to using a randomized withdrawal study in this context?
Yeah, we have direct dialogue and feedback with the FDA on the package. From a pre-NDA meeting feedback, we have that in terms of what the package will be, which will be three positive, adequately well-controlled trials. ADVANCE-2 will also be part of the package. That's a very robust package. We also have a standalone safety database in the patient population, which will be part of that. That pre-NDA meeting feedback is consistent with the feedback we've been receiving from the division from the start of that program in terms of what we need, which is two positive, adequate, and well-controlled trials. There can be different ways that we provide those, meaning different trial designs, and the standalone safety database.
So we'll be showing up with more than was requested that we provide for an assessment, which we are pleased with. So-
Kind of a follow-up question to that is sort of what is the incremental information and evidence that a randomized withdrawal study sort of adds to the package? I guess, is it adding kind of the long-term efficacy picture?
Sure. So the incremental evidence besides feedback we've received from FDA is what you can't do with randomized withdrawal designs is detect longitudinal change, right? But you can detect if the drug is working, right? And then the other thing you get is maintenance of effect-
Mm-hmm.
or treatment duration. So we'll, the package will include trials that provide data on those different elements. So, right, longitudinal separation or treatment effect and just overall treatment effect, prevention of relapse, and maintenance of effect. So we feel very good about the questions that the agency may have, and the data we'll have to facilitate their analysis. And so, in terms of other information, right, there's, you know, we tend to. This is, outside of feedback we've received, but there's precedent even within the division for randomized withdrawals for initial approvals, like take Spravato, right? So that package is comprised of or has a randomized withdrawal design.
You can look at written guidance in terms of substantial evidence of effectiveness or trial designs for controlling placebo response and things like that. So there are a variety of data points beyond kind of the feedback we've received, and it's not just meeting feedback. It's in the whole program we were developing in consultation with FDA in terms of overall what they would wanna see, the specific studies, the specific protocols, you know, analysis plans, statistical analysis plans, et cetera. So you know, and then with the latest interaction, we have alignment for the submission that we plan to put in.
Okay. Excellent. And I didn't mention this earlier, but if there's any questions, just raise your hand, let me know. We can work it in. I guess I also have a question just around the kind of primary endpoint for agitation, so the CMAI. How important are the various subdomains of CMAI to the FDA?
Sure. The question is maybe twofold. So one, what we've aligned to with the FDA, and this has been consistent throughout the program, is it's the total score.
Okay.
So the primary endpoint in the analysis and what we're looking at is the CMAI total score. The other element of it is the patient population, right? And that is dementia of the Alzheimer's type, so Alzheimer's disease dementia. So that's also been very consistent within terms of who we're enrolling and the target indication. We feel good about both of those elements. And then, again, if you're looking at external kind of information. We were talking about brexpiprazole, and that approval, I think, is also informative with respect to FDA, the total score on the CMAI.
As precedent, that's what they use, yeah.
Yeah. That, so I think it's informative there and, you know, how, you know, we tend to think of not rely on precedent as, as the strategy, but it's-
Yeah.
-it's informative.
Yeah.
Yeah.
Okay. Well, there's a ton to get here, but I do want to ask one more AD agitation question before moving on.
Sure.
I think, I believe earlier this year, Axsome increased its Auvelity sales force and MDD. I guess, how do you think about kind of the sales, any congruency in that sales force and, like, what would you need to do to the sales force to sort of optimize the commercialization strategy and adaptation?
Yeah, sure. So maybe just taking a step back, we initially launched Auvelity with 160 reps. Last year, we added 100 to get to 260, and then most recently, we expanded the field force by 40 to get to roughly 300. So, with an approval, we would anticipate that we would have a, an addition to the, the current MDD team, the current Auvelity team. So we would add, likely add ADA to the bag, Alzheimer's disease agitation, to the bag of the current, the MDD reps.
... along with having a more distinct LTC, long-term care community, sales force, and potentially do an additional ad on top of that.
Okay. Yeah, great. So maybe we can move into Auvelity and MDD and kind of that commercial launch. You know, I think you, you've kind of given us some guidance around what peak sales could be. Now that you've had multiple quarters, and you have this bigger sales force out there, like, I guess, do you still have confidence there, and sort of what would give you the confidence to maybe narrow that guidance? I don't know if it's official guidance, but
Sure.
Yeah.
Sure, so maybe take a step back. The MDD peak sales is $1-$3 billion. As I mentioned in my introductory comments, we're already tracking at close to $500 million, so very pleased, 11 quarters in from launch, and really even taking a look at comparing Auvelity to other MDD drugs that have launched, we're outpacing them, so super pleased with that. I think as it relates to guidance, that's something that we will take a look at. There's a lot of levers being pulled that we'll discuss, but we talked about the field force expansion. Just most recently this quarter, we announced 28 million additional lives being covered for Auvelity, getting us to 83% overall covered lives, which is great, and we're optimistic that number is gonna continue to improve.
And then, as importantly, we are investing in the brand with doing a national DTC campaign, which is gonna be starting imminently. So all of that will have additional levers to further grow revenue. And then, you know, as it relates to guidance, I think that's something that we'll let the numbers speak for ourselves, and then we'll update guidance accordingly.
Okay.
It probably, you know, not probably. It ties to where we see kind of steady state dynamics netting out in terms of, hey, where do you see average or standard access considerations, right? Front line, first line for switch, things like that. So, and the number of lines that, the number of patients that correspond to that, that'll really point us into, you know, into maybe allowing us to tighten, but we feel very good with that range.
Like, we're very comfortable with that range, where as Nick said, as where we are now, and so I, I think in our mind, it's, it's where we go from there, and that's coming together now just on the access side, on the sales force side, getting to, kind of target ranges for number of lives covered and also quality of coverage. And, and so we'll keep providing updates as, as we move forward there.
That's a really interesting point, and I guess, do you have line of sight as to who is using Auvelity? Are they front, like, you know, kind of the split between front line-
Mm-hmm
... versus switch?
Yes.
Yeah.
Yeah. So it's first line, first switch, so first and second line. It's about 50% of the scripts right now, and it's just over about 15-16% first line, and then the balance is second line, and then it kind of goes from there into third line and beyond.
Okay.
So we really like that, especially for how early it is in the launch, and so we think that bodes really well, and you know, for options for HCPs and patients, and also just in terms of long-term growth for the brand. With the sales force expansion, right, that allows us to increase reach and frequency and go further out into primary care. The initial focus of the launch was psychiatrists, and of course, we're still engaging and educating psychiatrists, but now we can go further out into primary care, which then also aligns nicely with the increases in quantity and quality of coverage, covered lives, and then also some of the things we'll be doing to help drive awareness with respect to DTC advertising and things like that.
We have a nice confluence of, you know, functional activities and awareness that's coming together now and then moving forward.
You know, with that sort of broadening of the footprint and the kind of the commercial scope, and kind of what you were speaking about in terms of the patients and sort of the earlier line, should we be modeling, like, a improving duration of therapy? How should we-
We're still watching that.
Yeah.
It's coming in now, you know, it's outpacing what you typically see with persistence and compliance for SSRIs, but it, you know, in our minds, it's still somewhat early, especially when you're trying to drill down into lines of therapy when you have less data, right, and so really seeing what that number crystallizes in terms of, you know, steady state persistence and compliance and with access changes still coming online, it's still a little bit early for us to offer commentary, but we like what we're seeing so far. Yeah, that's something the team is watching closely.
Okay. And I guess maybe one more kind of adoption question. Sort of what do you envision sort of driving the biggest sort of incremental adoption? Is it just going deeper into your existing sites, or is it kind of what you were explaining earlier, expanding that footprint?
It's a great question. I don't know if there is, the commercial team may have a, the coefficient for each function of what is-
Oh
... what is a better growth driver, but you know, what we know is really important is trial, so when clinicians try the product, a few instances of trial leads to clear adoption, and so that's you know in terms of the field force educating HCPs, when we see trial occurring, then you see adoption following, so that's a very good predictor that we've seen so far, but again, we haven't shared numbers, but I think they're all probably meaningful in terms of additional coverage coming online, expanding the sales team, and then awareness-
Okay.
From Day two to-
Maybe just to add, I mean, to give some sense of where we are, being even at $500 million annualized sales, roughly, we're only at 0.16% market share of the total market, so we are just scratching the surface. There's a lot more to go.
Okay. That's good context. And when you say trial, that's a... Is that a physician office trying this out for the first time, or is this putting a patient on?
Yeah, put a patient-
Okay.
A patient, you know, trying a sample-
Yeah
... or a script. And the feedback we're getting from clinicians, HCPs, KOLs is that the outcomes are differentiated in terms of patients, you know, and depressive symptoms of depression improving quickly, robustly, and then with a safety and tolerability profile that's distinct from you know, what you typically see.
Mm-hmm.
Seeing that is, you know, clinicians seeing that seems to be very compelling.
Great. Okay. Maybe just one last question, kind of blocking and tackling on this, on this topic. I guess, gross to net discounting, where, where do you kind of see that, sort of, at steady state?
Yeah. So, steady state for this year, we've shared that Q2, we were in the mid-fifties. That was a slight improvement from Q1 in that mid-fifties range. We did share for the back half of this year that we would expect to remain in that mid-fifties range. Reason being is, with that 28 million additional lives coming on board, access is gonna really improve for them. Patients are able to get the, get the drug. We don't anticipate a degradation of that mid-fifties, so we kind of feel like that mid-fifties is our high point for this year. So improved access and net price basically staying stable, potentially improving. We'll see how that, how things are adjudicated or how these lives are adjudicated in, in Q3. Steady state, we've also shared that we, you know, look to stay in that mid-fifties.
Okay, excellent. Any other questions on MDD? So let's turn to migraine Simbrivo. Early days, of course-
Yes
... but, I guess, you know, they are early days, but give us a sense, what are your goals exiting this year? Like, what do you want to achieve from the launch perspective?
Sure. So it is early days, but we're, you know, so we're just taking off the launch pad, so to speak. But one of the things we're looking for is just feedback from clinicians in terms of how the product does in a real-world setting, right? So, and does it tie to the clinical data that we generated? And so far, the feedback that we're getting, again, it's very early, but it is positive feedback that the drug has robust efficacy and which is what the need is for patients right now, is differentiated efficacy. And then also, that the tolerability profile is conducive to utilization. So that's helpful, and we've started the launch with a very discreet sales effort.
So it's a hundred reps. They'll be targeting the bulk of headache centers in the U.S. So it's about a hundred headache centers. That's the primary area of focus, and of course, there are adjacent, from a territories perspective, other targets that are part of that, but it's going to be educating those potential prescribers about the product, seeing utilization, and then seeing how our infrastructure, the sales infrastructure facilitates. So there will be sampling. There will be a savings card to help patients get product if a script is written, especially as we navigate from the NDC block phase to coverage in both the commercial and government channels.
Already, we've secured coverage in both channels, so it's about a third of lives are covered already, which is great. Then the work underway, there's another thing we'll be looking for, or that one of the goals, is driving continued improvements in access, just in terms of lives being covered. But in the meantime, we'll want to be seeing that patients, you know, appropriate patients who get a script, that they're able to fill it-
Mm-hmm
... and that's done relatively easily, and then we'll go from there, but so far, yeah, we're pleased. You know, it's just two months now, but we're pleased with, again, launch, so to speak, and we'll definitely be keeping everyone updated, you know, here on out.
Okay.
Yeah.
I guess just on the sampling program, maybe just a couple questions around that. Maybe this is too early, but do you have a sense for kind of the rate of conversion to paid scripts in that setting, or is that really just dependent on just getting payers in line?
It's probably too early to offer anything that would be helpful or precise. Yeah, no, we'll be watching that. I think when there's enough data to offer commentary there, we will. But definitely what you see, you know, you have higher gross net discounts here because of how the class is managed. And so you do have there are a variety of patient support, you know, across the class, not just Simbrivo. But what you see is, you know, there are very robust patient support systems or, you know, patient savings cards and things like that that are in place to help facilitate that.
So that'll be present, and but you do want to definitely start to see, you know, covered claims coming through.
Okay.
So, yep.
I guess, through your sampling program or through your other checks, do you have a sense for what patients are early adopters, what migraine patients are early adopters of Simbrivo?
I mean, just when you're, because of where we're detailing and educating headache centers, they tend to be later-line patients, right?
Okay.
And so that makes sense in terms of, from a coverage perspective, in terms of, you know, ease of writing a script, and those offices tend to also be familiar with, right, the classes managed with PAs, new to through the NDC block and also through covered, branded agents that are covered on plan. So the, you know, PAs are ubiquitous here, and so you want to start with offices that have the infrastructure and support, you know, office staff in place to be doing those, and but then those also tend to be later-line patients.
Okay.
So that, you know, that is not, though, the ultimate steady state kind of niche that we expect to be living in. We, you know, we expect the product to have, you know, based on the clinical data and early feedback, that the product has much more potential utility or optionality for HCPs earlier in treatment, right? And so, you know, we'll see, but we, you know, again, that speaks to the feedback we're getting on from an advocacy perspective, that it's the advocacy is noteworthy and in a tolerable fashion, so.
It's a similar playbook that we did with Auvelity, right?
Mm-hmm.
So we're focused on headache centers, high-decile doctors. And for Auvelity, we launched with 160 reps, which by any standard was low compared to some of our predecessors, but we focused on high-decile psychs, and then we're slowly branching that out and going to general practitioners.
Okay, makes sense. And then maybe talk about the patent runway this gives you.
Sure. So, for Simbrivo, the patents go to 2041, and, you know, we feel very good about that and a variety of claim strategies. And, you know, one thing that we can share is that there was a Paragraph IV filer, which is as expected, and so that process has now started. Those gears are turning. It's and, you know, we obviously have that experience with Auvelity and Sunosi in terms of moving that along, and so that's great, and we'll keep it moving. Obviously, we don't comment on specifics there, but the runway is to 2041, and we feel really good about the patent portfolio that's in place.
Okay, excellent. Let's move on to Sunosi then, solriamfetol. I guess from a commercial perspective, so this is being approved, this is being used for obstructive sleep apnea and narcolepsy. Which one of those is kind of the bigger opportunity in your mind, or are they both important?
They're both important. I think the balance of scripts right now, about two-thirds are coming from OSA, and so EDS in OSA. And you know, that product, since we acquired it, we've been driving steady growth, and you know, we're pleased with that. We think that'll continue. We are really excited about other potential indications that we're working on. So we're exploring the product in four other indications. That's ADHD, MDD associated with excessive daytime sleepiness, binge eating disorder, and shift work disorder. And so those trials and programs are at various stages, but they're all moving along, and I think those are potential key potential catalysts by next year and beyond, which we're very excited about the...
But one thing about Sunosi that's really interesting is, you know, it's approved for improvements in excessive daytime sleepiness in the indications you mentioned or the areas you mentioned, but the feedback from clinicians is that patients do very well globally, and which is great and, you know, very tolerable. And so that's where a lot of our excitement about other indications come from.
Okay. Actually, you know, maybe you could talk about some of the ADHD data that you've generated there. And maybe mechanistically, like, how is this working in ADHD?
Yeah, so it's a norepinephrine reuptake inhibitor and a dopamine and norepinephrine reuptake inhibitor, and so that, you know, that's what has been implicated, right, in ADHD. And so far, mechanistically, there's the mechanistic rationale. There was the KOL feedback in terms of their perspective, you know, in a real-world setting of how the product does. And now we have clinical data from the phase III FOCUS trial that we ran in adults, and that study was positive. And so the next step there for us is to conduct a study in pediatric adolescent patients. So that's the other study we need before we can file, and you know, we're pretty excited about that and, you know, its current stage of development except for that program.
and so yeah, the next update there is launching the pediatric adolescent trial.
And do you have a sense for, like, the dose that would be needed for pediatrics? Is it different from adults?
We haven't disclosed that dose yet, and I think you could expect that from us probably, upon, say, trial initiation.
Okay.
But yeah, you, there are considerations from a dose perspective for those younger patients. Yeah.
Okay.
Yeah.
From a kind of commercial expansion, like, what kind of increase in top line could that potentially bring in, like ADHD?
Yeah, ADHD, I think from a peak sales revenue, we said $1 billion-$3 billion. I think that's the... You know, that's why we love the asset. The current indication is maintaining, and it's actually a truly healthy business, just as a standalone, in those two indications. But for ADHD alone, we believe it's a $1 billion-$3 billion dollar-
Mm-hmm.
Potential sales.
Okay.
Yeah.
Excellent. And maybe just kind of going down the list, so you mentioned a couple of these indications that Sunosi could be applied to, but, like, so for excessive daytime sleepiness associated with MDD, what is the goal there? Is the goal... Is, is it to just improve sleep, or would you also look for some impact on depressive symptoms?
Yeah, no, the primary would be impact on depressive symptoms.
Okay.
Like, let's say, like, looking at MADRS scores as the primary endpoint. It would be who you're enrolling in the indication, which is patients with depression who have excessive daytime sleepiness. It wouldn't be the other way around, where it's people with excessive daytime sleepiness who also have you know, a component of depression and that you're looking for sleep changes. Here, it's your... It would be for major depressive disorder, but then it would. In a way, it's a precision-based approach, where it's MDD, but say, not with anhedonia, but rather MDD with excessive daytime sleepiness.
Gotcha.
Yeah.
Are you looking at sleep scores as well as secondaries?
So, for the studies, we haven't, you know, disclosed key secondary endpoints and things like that, but obviously, you would be looking at different sleep measures, given the indication. So yes, you would, but we haven't shared specifics.
Okay.
Yeah.
Okay. And just a couple more minutes left. I want to hit a few of these other-
Yeah
... programs. So, AXS-12 in narcolepsy, what's the value proposition there, and kind of what are the next steps, inflection points there?
Differentiated product profile, so just another distinct treatment option for patients, and so clinical work is done, and so what is the overall product profile? We looked at so NT1 patients, so narcolepsy with cataplexy, and for us, the primary endpoint that we focused on was cataplexy. We also looked at sleep. We looked at cognition and saw improvements in both there, so that's some of the kind of, like, the efficacy profile. Tolerability profile is very nice with respect to what's approved and other programs in development, so it's distinct there. Daytime dosing scheduling is distinct from a approved product, so it would be a differentiated treatment option, which we like, and you know, it is an orphan indication, so it has orphan drug designation.
So there would be the potential, you know, commercial dynamics around there with respect to regulatory exclusivity and say, pricing and market access dynamics, and so we like that. And then in terms of next steps, mentioned the clinical work is done, so it's NDA submission, which we've guided to for 4Q.
Great. And presumably, if that does get approved, it's an easy add-on to their, our sleep field force.
Yeah.
Oh, okay.
So super synergistic-
Yeah
To the Sunosi team.
Yeah, exactly. So just high overlap with the established commercial infrastructure that we already have.
Okay. Maybe just one last question. So Axsome has a lot of different programs, a lot of R&D going on. You also have some top-line revenue coming in. I guess, philosophically, how do you think about the need or the desire to maintain profitability versus just investing in the business?
I think our focus, our number one focus is top-line growth, top-line sales growth. We're able to invest in the entire business. Our focus right now is top-line growth, then the next one would be the cash flow positivity and then to ultimate profitability. And I think it, you can see our, our improvement in cash flow in the aspect that if you take a look at our P&L on a cash basis alone, and take out any one-time items, first half of this year, that number would be about $50 million loss. Last year, we, it would've been around a $100 million loss. So we've improved by more than 50% year over year, just, from first half of 2024 versus 2025.
So again, to answer your question, Ben, the focus right now is top-line growth, and we're able to invest in all aspects of that.
Great. All right. Thank you all very much.
Thanks for having us.
Thanks, man. Appreciate it.