Good morning, David Amsellem again from the Piper Sandler Pharma team, and welcome again to the Piper Sandler Healthcare Conference. With us is Axsome. A lot to talk about, and with us is Herriot Tabuteau. Thanks so much for joining us this morning. Let's just dive right in. There's a lot to talk about with the commercial business and the pipeline. What I wanted to do, as a starting point, is talk about the sales force expansion earlier this year, and how that better enables the company to support products beyond Auvelity, and how that furthers your vision of building a multiproduct company. Wanted to go through that and then have a few follow-ups. Great. First of all, thank you, David, for having us here at the Piper Sandler conference. So, as you mentioned, we did make the decision to expand the sales force. That sales force expansion is well underway, and, you know, we do expect to have all of the hired folks in the expansion on board by the end of the year, and fully trained by the first quarter. The reason for that is to take advantage of the opportunity, which is in front of us. We've seen great reception and great demand from HCPs, and also, with that is greater need to have folks out there to properly educate the HCPs on the appropriate usage of the product. So we're really excited about that and what it means for Auvelity. And if you think about it, with the 162 sales reps that we launched the product with, that had allowed us to reach, you know, roughly 26,000 HCPs, and with the additional 100 sales reps that we've added on, that will allow us to reach 44,000 HCPs. So that's on the Auvelity side. One of the things that we really like about our business model is the potential for operational leverage. So, so as you, as you alluded to, there is the opportunity to use that expanded sales force for other potential products and indications that we would launch. So we are a CNS-focused company, and if you look at our pipeline, we do have additional products and indications in neuropsychiatry. Mm-hmm. So, the same HCP customers that we are targeting for Auvelity will also be appropriate for, let's say, things like Alzheimer's disease agitation. Mm-hmm. So the behavioral symptoms of Alzheimer's disease are treated by psychiatrists, ADHD, which is an indication for solriamfetol, as well as binge eating disorder. Those are both, you know, primarily psychiatric populations. And, you know, even when you think about the current indication for Sunosi, which is excessive daytime sleepiness- Mm-hmm. In patients who have OSA, it does turn out that a good proportion of the writers for Sunosi, for that indication, for the current indications, are also psychiatrists. Not that we'll be right now making the decision to use that expanded sales force for that current indication, but it does speak to the potential for the business that we're building in the near term, as well as in the intermediate and long term. Yeah, that's helpful. A couple follow-ups. So number one is, should we expect further headcount expansion down the road as these opportunities that you alluded to bear fruit? So that's number one. And then the second question, follow-up question is, talk about your focus on general practitioners. Certainly in major depression, there's a big audience of GPs that write antidepressants. So what is your level of focus there? So in terms of the sizing of the sales force, you know, as it stands with the expansion, we think it is appropriately sized. Now, it is natural to always reevaluate and tweak, either adding or reducing, as appropriate, the sales force. So we're data driven, so we'll be looking at the data. The with regards to the number of PCPs and general practitioners, the expansion does allow us to target more of those primary care physicians. Mm-hmm. In terms of quantifying that, if you think about it, you know, before the expansion, our target list included probably around 10,000- Mm-hmm. Nine or 10,000 primary care physicians, and now with the expansion, it doubles that. Okay, that's helpful. Let's talk about specifically on Auvelity, the level of DTC investment. Certainly, MDD is a promotion-intensive setting. Should we think about your DTC activity in 2023, this year, being generally steady state? Is there going to be more expansion of DTC down the road? How do you think about that? The way that we think about that is one, there is some baseline level of DTC promotion which is ongoing. When folks think about, I think generally historical or traditionally DTC, people have thought about linear TV. Mm-hmm. But as you know, a lot of promotion has now moved to other platforms, and so that has been ongoing. So that's always been part of our promotion. It's currently part of our promotion. Will we expand on that? Yes, at some point, you know, we will. And what we want to do is we want to make sure that we're ready to do that. Mm-hmm. So the work is underway, the assessments are underway. We want to make sure that we do it in a rational way, and we want to make sure that we do it at a time when the return on investment will be appropriate. Okay. Wanted to move on, also on Auvelity to the reimbursement landscape. I'm not going to ask a gross to net question. And more broadly, interested in how much more contracting you are looking to do, both commercial and government payers. And I'm also interested in, you know, the extent to which patients are stepping through or having to step through multiple antidepressants in order to access the product. And where I'm going with this is sort of the extent to which getting a script is hassle-free. Mm-hmm. Sure. So if you step back, right now, you're roughly a year into launch. We have about 70% of covered lives. So that's in total. And the way that breaks down is on the commercial side. We have 48% of covered lives. Mm-hmm. On the government side, we have 100% of covered lives. So, that's the current mix. Mm-hmm. Negotiations with commercial payers continues, and we would fully expect that 48% on the commercial side- Mm-hmm - to increase over time. And so we, we would expect to see a, a meaningful increase in, in 2024. And, with regards to, you know, what that coverage looks like- Yeah - which is, I think, the second part of your question, in terms of numbers of steps, it does vary. Yep. It varies significantly among plans. With some plans, you know, currently, it's no steps and... Yeah No PA. And with other plans, it is a PA and anywhere from zero to three steps. Okay. And you're right, you know, the goal is to make sure that we ensure as easy and straightforward access for patients as possible, while also making sure that we get appropriate value for the clinical benefit- Okay - of the product. Okay. So I wanted to switch gears to Alzheimer's agitation with additional data on the horizon. But I wanted to step back and ask you how you are framing the opportunity here. And, you know, the way I think about it is, on one hand, you have a lot of agents, including atypical antipsychotics, that you use off-label here. On the other hand, lots of limitations for those agents and, up until recently, nothing approved. So I guess the question here is, what's your take on the opportunity here? How do you think about that? We think, that there is a significant unmet medical need- Mm-hmm - and a large patient population. So, just to review, 6 million patients who have Alzheimer's disease, the vast majority, probably up to 70%, experience agitation. Mm-hmm. It's also a rapidly growing patient population. We do expect that 6 million to go to 14 million patients by 2060. And it is a significant problem because we do know that the behavioral symptoms of Alzheimer's disease, especially agitation, are oftentimes much more troublesome... Mm-hmm and bothersome to patients and their families than the cognitive symptoms. Mm-hmm. The agitation is one of the major reasons for early nursing home placement. And the atypical antipsychotics, which you mentioned, which are used to treat Alzheimer's disease agitation off-label, they are problematic because they all carry a black box warning, specifically against their use in elderly patients with dementia. So this is basically Alzheimer's disease patients. Mm-hmm. The reason for that is that they've been shown in meta-analyses to significantly increase the risk of mortality. Mm-hmm. So we like the product profile, thus far, of AXS-05 in Alzheimer's disease agitation. Mechanistically, it is different. Mm-hmm. What we've seen also is that it's well-tolerated. It results in a rapid improvement in Alzheimer's disease agitation. From a safety perspective, we really like the profile as it compares to atypical antipsychotics. So a lot of the baggage which you have- Mm-hmm with those agents, because AXS-05 is mechanistically different, you know, obviously it would have a different profile. Yeah. It, this is another high-level question. You have companies, like, like Karuna, for instance, that has a an Alzheimer's psychosis program for the, the, you know, the muscarinic, for the muscarinic, agonist. And, and I think with AD psychosis and AD agitation, there's some degree of overlap. Obviously, they're distinct, but I, I'm just wondering out loud, as over time, as we see more agents come into the market for AD psychosis, I know it's not agitation, but does that in any way change how you think about the opportunity? No, it does not. So if you think about an Alzheimer's disease patient, an Alzheimer's disease patient does have a lot of comorbidities. Sure. But the neurobehavioral symptoms are pretty distinct. Mm-hmm. One would treat whichever one is most bothersome to the patient. So in other words, which one brings the patient to clinical attention? Yeah. So, again, this is a high unmet need, and you do have a need for new agents, actually approved agents. In the case of Alzheimer's disease agitation, there's only one. Mm-hmm. So yeah. We think that if anything, bringing to light more attention on the behavioral symptoms of Alzheimer's disease is a good thing for patients. I know that you referred to... This is a commercial question. Mm-hmm. You referred to the AD agitation program as AXS-05. But I just sort of wonder out loud, are you gonna brand this differently? It is a Medicare Part D. Mm-hmm. primarily Medicare Part D market. So do you brand it differently? Do you price it differently? Help us understand how you're thinking about that. Those are all great questions, which, our clinical team and our commercial teams are thinking about very carefully. We do have options. Yep. And there is precedent. However, that is a determination which we have not yet made, but which we are thinking about very carefully. Okay. So let's switch gears, digging more deeply into the pipeline, solriamfetol. And I'm particularly interested in your ADHD and binge eating disorder program. You know, I kind of look back at what Shire did for Vyvanse with not just ADHD, but also binge eating. I kind of think that at first glance, maybe you're borrowing from that playbook. So is it safe to say that you're sort of trying to position solriamfetol as perhaps a cleaner Vyvanse, although, you know, not a stimulant, but a, you know, effective but cleaner? Is that sort of how you're thinking about solriamfetol generally? One of the things I think we really like about solriamfetol- Mm-hmm. -is the clear differentiation in terms of, magnitude of clinical effect- Mm-hmm In the current indication, for example, in excessive daytime sleepiness. So we really like that. And the other thing too, that we have shown with solriamfetol is the improvement in cognition. So we read out the SHARP study, which was looking at specifically patients with excessive daytime sleepiness- Mm-hmm ... and obstructive sleep apnea, who also had cognitive dysfunction. Mm-hmm. And so that was a prospective placebo-controlled study that was highly statistically significant, showing a benefit on cognition. So the potential profile of solriamfetol is potentially a drug which has a very clear benefit, very, very strong efficacy- Mm-hmm -but, at the same time, does not have the limitations of stimulants. So taking that to ADHD- Mm-hmm The current drugs that are approved, on the one hand, you know, you have stimulants which are known to have very high efficacy, and you know, large effect sizes. Mm-hmm. But, the known limitations of stimulants from a safety and tolerability perspective. And then, you do have the non-stimulants, which do not share those limitations, but which, have a lower effect size in terms of efficacy. So with solriamfetol, there is the potential- Mm-hmm -to really fill that need, which is, which would be in the middle. So, the known tolerability profile of solriamfetol, and it combined with potentially a, a very strong efficacy profile. Do you see a better fit in pediatric or adult ADHD, or equally both? Uh, uh- I know we don't have the data, but- Yeah, and we- Yeah ... we don't have the data, but drugs that typically work in ADHD work in both- Yeah pediatric populations as well as adult populations. The larger. So of the 17 million patients estimated in the U.S. who live with ADHD, the vast majority are adults. So roughly 11 million are adults, and 6 million are pediatric patients, and those pediatric patients eventually become adult patients. So that, that's the landscape. So the larger part of the market definitely is adult patients. Mm-hmm. However, you know, we do intend to study the drug in pediatric patients. And our NDA for that indication would include both populations. Okay. Competitive questions. The brand non-stimulant now that's, you know, been launching is Supernus' Qelbree. And again, I mean, you don't have your pivotal data, but what's your view regarding the potential for differentiation versus Qelbree? So as you—you just said it. You know, we do need to be careful and wait until- Sure. We have the full clinical profile of our product in ADHD before making any kind of pronouncements. But this is a very large market. Sure. There clearly is a continued need for new products that work better- Mm-hmm. -and that are also well-tolerated. So we look at solriamfetol, what do we like about it? We like the known efficacy and the strong efficacy, in the current indication as compared to, let's say, drugs like, other wake-promoting agents- Mm-hmm. like methylphenidate and armodafinil. We like that. We like the differentiated mechanism of action. Mm-hmm. So it is a dopamine and norepinephrine reuptake inhibitor. It is also a TAAR1 receptor agonist. So we really like that differentiation. And we also like the link of those mechanisms of action to improvements in cognition. Mm-hmm. -which have been demonstrated both in non-clinical models and then more recently, we've demonstrated that in patients. So let's switch gears to reboxetine, in cataplexy and also EDS. I know that data's coming in the not-too-distant future. So I wanted to ask you a question about the commercial landscape. We do know that in narcolepsy, there are dual reuptake inhibitors like venlafaxine and duloxetine that are used off-label for anti-cataplectic effects. So I guess with that in mind, where would reboxetine fit in commercially? The fact that the agents are being used in narcolepsy speaks to the need. Sure. Right now, there are currently only two agents, so two chemical entities, that are approved for cataplexy. Mm-hmm. So you have the oxybates, sold under various brands, and then you also have pitolisant. Mm-hmm. So we like the profile of reboxetine. We've shown in the Phase II trial, we've shown very strong efficacy in cataplexy. And also, we showed a very strong signal in terms of cognition as well as excessive daytime sleepiness. And we're looking forward to the data, and we think that should the product be approved, it would make a meaningful addition to the treatment landscape. Now, I know your primary endpoint is cataplexy attacks, but is the goal ultimately to have a label that encompasses both cataplexy and EDS? Is that ultimately, you know, what is, I guess, for lack of a better term, commercially the most viable? So the approach that some sponsors in the past- Mm-hmm have taken as it relates to narcolepsy is to target specific symptoms individually, and that can be done incrementally over time. And so, as you know, you know, with different indications for the same patient population, you want to make sure that you approach things in a very goal-oriented, specific way to get the product approved. Mm-hmm. So right now, our primary indication is cataplexy, and we're really focused on that, and we think that if we're successful, we'll have approval for the product, and it'll be available to patients. So, esreboxetine, wanted to make sure I asked you about that, in fibromyalgia. Another sort of commercially oriented question. Curious how you're thinking about the role here commercially and its potential, given that you've got other agents with noradrenergic activity, Cymbalta, duloxetine certainly comes to mind. Mm-hmm ... that are used both on and off-label. So how do you think about that? It's the clinical profile. Yep. So it's a large patient population, right, that suffers from fibromyalgia. So 5-7 million patients, so if you think about that against the backdrop of only three agents- Mm-hmm -being commercially available, high unmet need, of a lack of innovation in the space. We really like the clinical profile of esreboxetine or AXS-14 thus far. So in two clinical trials, it has shown a strong effect on pain. It has shown significant improvements in function. And then, in addition, it has shown significant improvements with regards to fatigue- Mm-hmm -which is a very difficult symptom to treat for in patients with fibromyalgia. So, we think it's very differentiated and of the three products that are currently approved, they do not have as strong of a profile across as wide a spectrum of symptoms. Before we wrap up, I wanted to pick your brain real quick on how you're looking about commercializing all of these opportunities that we've talked about. We haven't even talked about AXS-07 and migraine, but I guess, are there any assets that you would look to monetize or be opportunistic on? And then, you know, conversely, what about further in-licensing activity along the lines of what you did with Sunosi? How do you think about that? How big of a priority is that? Yeah. So, we've built an organization- Mm-hmm ... that could be leveraged, a commercial organization that could be leveraged for all of the products that we are developing. So we really like our digital-centric commercialization platform. We like the way that it's performed thus far for Auvelity as well as Sunosi, and we're gonna leverage that infrastructure. We think that that's the way to generate the most value. We will continue to obviously monitor our business, and we're not afraid to make choices or course corrections along the way, but our goal is to maximize shareholder value. With regards to other opportunities that we could in-license, we again, we're flexible, and we're always thinking about the business. One of the things that we're fortunate to have right now is a very rich and broad pipeline. Mm-hmm. There's really no need to run out and do anything. However, you know, we've shown in the past that if the right asset comes along with the right fit, and it makes sense from a value perspective, that we're ready to act. Great. All right, well, we're out of time. Ari, thanks so much for joining us. Thank you to the audience. Thanks, David.