Next company presenter, Axsome Therapeutics, and Mark Jacobson, Chief Operating Officer. We got Nick Pizzie, CFO as well. My name is Jason Gerberry. I'm one of the SMID Biotech Analysts. Guys, thanks so much for joining us. Thank you very much for having us, Jason. Good to be here. Happy to field any questions you may have, but obviously a really good start to the year for us so far. Yeah. So, I mean, I think, you know, in terms of Auvelity and the commercial uptake, that's been solid. The patent settlement, I think, has taken a part of the discussion out that you probably do not want to have to have with investors. And you have got like a better line of sight in terms of long duration of asset and some clinical development for other assets not named Auvelity, including SYMBRAVO approval. So we have got a lot to talk about. Maybe we will kick it off just with Auvelity and MDD. You know, solid quarter. Where do you feel like you are at in terms of the launch cycle, in terms of added initiatives to try to grow that? How do you think you are comping relative to other MDD launches at this similar stage of the life cycle? Sure. Yeah. We're a bit past two years from launch, and we're still very much on growth trajectory and continued launch and like Q1, ease with that execution. We're really looking forward to the balance of the year. There are a number of initiatives and activities underway that we think will continue to drive growth, and one of which has been implemented, and that is the field force expansion. We recently increased the field force to about 300 reps. That was completed in the Q1. We're just starting to see impact in terms of NRx. We'd expect that impact in growth to continue through the balance of the year. Typically, what we saw with last year's expansion is that changes really start to manifest three to six months after expansion. That's one category and one potential growth driver. Another is just continued execution with respect to coverage. The number of lives covered and the quality of coverage. We expect to see and drive positive developments on that side of the business. Third, in the second half of this year, we'll be launching a national DTC campaign. Those are kind of classic categories that can catalyze continued growth. We'd expect that. Also, we would just continue to expect growth trial, HCP trial, and patient trial. When we see that, we see good uptake with HCP and adoption. We expect that kind of underlying dynamic to grow. Since you've launched, you've stepped up, I think, some of the resourcing behind it in terms of sales reps. You've got planned DTC spend coming in. I imagine with like a lot of different brands, you reach a point of like, all right, this is sort of fully resourced, and we can get to a point of like incremental growth and starts to become a source of positive operating leverage in the model. Right now, I get the sense that you're kind of investing to drive a better area under the curve with a better top line for the longer term. That's a good trade-off. Do you feel like with some incremental amount of investment for DTC this year and where the sales force is, we're kind of getting to that more fully resourced level and then we start to get some more operating leverage going forward into 2026 plus? I think we'll see further efficiency from the field force. As Mark mentioned earlier, we just completed the expansion in Q1 of the 40 reps. We are seeing the NRx growth nicely. As payer dynamics change or evolve, we would expect to see further growth from those additional covered lives. The DTC campaign, as Mark mentioned, we're planning for a national campaign that we would anticipate have a very nice ROI. Seeing that operating leverage in the P&L, I think we will, we're seeing it now. Revenue growth is outpacing our operating expense growth across the board. We will anticipate to see that in rest 2025 and 2026. Yeah. I don't know though if we see on the near horizon where there's diminishing returns with respect to driving growth. I think we still expect to be in growth mode for the course of the year. Okay. Yeah. I mean, a lot of peer brands, I look at like AbbVie, Vraylar, right? DTC has been a very seemingly important element of that. Most of Vraylar's utilization is in depressive states of the bipolar and unipolar depression. When you look at sort of the comps and how promotionally sensitive do you think MDD is and how important this could be as a growth accelerant to the franchise? I think it's promotionally sensitive. What we'll continue when we scale to 300, and that gives us flexibility for continued work within MDD. If additional potential indications come online, there's leverage there from a targeting perspective or overlap and potential targets and things like that. That's in-house already, so to speak. I think to your point, even within MDD or with potential other future indications, there could be scenarios where we continue to expand kind of the investment in the brand and the commercial infrastructure around the brand. Okay. And then as in a protected class, you have good government insurance right out of the gate. Commercial coming up, I think it's 68% on the commercial side or so. Where you at? I think there was some mention on the earnings call about the potential to improve the commercial side of the coverage over the course of the year. Do you feel like you have enough leverage now given how big Auvelity has gotten to where when you go to payers, you maybe were trying to maybe force your hand with a tougher deal that you can strike deals and kind of keep that sort of net pricing or gross to net as we think about it, right, within the range of your kind of steady state guide? Yeah. I think it goes to the efficacy of the product, right? Our strategy out of the gate negotiating with payers was always long term. As a reminder, our IP takes us through 2039. We were always being mindful of long-term value for the product, not getting covered lives day one or even day 365 to where we anticipate them to be. To answer your question, Jason, I think we're pleased with how conversations are going with payers. Currently, covered lives in the commercial space is at 63%. Just again, with the 300 team field force that we have, if we're able to improve those lives, we think it's benefit to the patients as well as to Axsome. Okay. Were you going to say something, Mark? Yeah. No, I didn't stop myself. I wasn't sure if it was going to be redundant. We haven't guided to a steady state expectation to say a certain number of covered lives, except to say that. In the government channel, essentially 100% of the lives are covered now. Our expectation for the commercial channel is that we'll be in line with what you typically see for us at steady state, which is north of 80% of covered lives in the commercial channel. That's the steady state dynamic for the class. We don't see any reason why we would be out of line with that. Yeah. Maybe to further that, 63% commercial covered lives, 78% overall. Importantly, as Jason, as you mentioned, our GTN in Q1 was in the mid-50s. What we shared to the street is that we anticipate that GTN did remain constant throughout the year. The reason being, you will see seasonality. However, as potential additional coverage comes online or also as payer access evolves, we would anticipate that would adjust the GTN accordingly. You may see favorability from a seasonality, but you may see an impact from additional covered lives or how utilization and management evolves. Maybe going from two steps to one step, but GTN would adjust accordingly. Yeah. I think consensus for Auvelity MDD is kind of at the midpoint of your $2 to $3 billion or so guidance. As we think about sort of the variables that can drive the bull case, right, to the higher end of that, how much of that do you think is in your own mind, as you guys think about the launch, just maybe faster coverage or how responsive the market proved to DTC? Is the proof points in your mind, maybe in the next 12 to 18 months, as to where you're at within that sort of growth trajectory? Yeah. I think that makes sense. What we see over the time frame that you suggested, how the growth curve changes or inflects, do you think that'll impact kind of where we've net out from a peak sales potential? Right now, the range we gave was $1 billion-$3 billion in MDD. That floor we're very comfortable with right now. It's really where you are above that. I think that's right in terms of outlook for the next year, year and a half, and how some of the growth drivers come to fruition and when they come online and the confluence of those, that they synergize. I think just another important consideration, part of the reason for the field force expansion is that allows us to have more engagement with primary care clinicians. We think that's really important in how utilization or potential prescribing dynamics in that group, where that kind of coalesces around. Right now, we're at about north of 50% first and second line use. So first line or first switch. If we see that continue in primary care and things like that, I think that'll also be another key for exactly where we net out from a peak sales perspective. Okay. Maybe shifting gears to the Alzheimer's agitation label expansion opportunity. If you can maybe just outline, you had data in December. I think you're indicating a second half 2025 filing and just some of the lag factors and where you're at with FDA in terms of, not with FDA, but where you're at internally to get that over the goal line. Yep. Right now, it's building the package. We completed the clinical program in December. Earlier this year, we announced the shared FDA feedback we had received for pre-NDA meeting feedback and meeting minutes. We're good there. We completed that part of the choreography, so to speak. Now it's building the package, writing the modules and assembling them, and guided through a Q3 submission for an sNDA. The data generation and the clinical studies, that's done. It's bringing it all together in a quality fashion. The team, as you might imagine, that's a key effort internally and a key corporate priority for the year. That's very healthy work going on, and we're excited about it. Yeah. There's, I guess, some debate out there, like FDA, some people would say FDA doesn't like randomized withdrawal studies. KOLs would say, "Hey, this is two studies with diverse study protocols." That's more robust evidence of efficacy. FDA has approved CNS drugs on the basis of randomized withdrawal studies. Can you maybe speak to any, I imagine there was some alignment with FDA before you even headed down this pathway around choosing the types of studies and the study designs that you did? Yep. Definitely. The very first study we did, that was ADVANCE-1 for the parallel group study. That study was positive. Once that study completed, we engaged with FDA, shared the results. That led to receipt of breakthrough therapy designation for the program. That was the start of the feedback for what the rest of the clinical program would look like. Since then, we've been continuing to engage with the FDA for what a package could and should be and what's acceptable. We feel very good about that. We have three studies to correct their different paradigms. We have three positive studies. We have looking at longitudinal change over a short-term period of time, like five weeks, that's the ADVANCE studies. We also have maintenance studies, so maintenance of effect. That's a randomized withdrawal design study. We feel very good about the package we have and also its congruency with the feedback we received from FDA in terms of supporting a filing for review. Yep. Okay. If approved, I mean, can you maybe frame this interview? I know you're looking at this as a supplemental NDA. We have seen other what we call indication stacking situations with other CNS drugs where drugs just step into the coverage, right, of the pre-existing indication. Yet, I think when we look at how the Rixulti launch is going, I think that there are some unique challenges to building out the ADA market. Maybe what have you learned from the early Rixulti rollout? Are those concerns about sort of a heavy lift on the market build side substantiated in your view? Yeah. Maybe take your own viewpoint. Yeah. So I don't want to speak too much about Rixulti, but if you just take a look at growth in channel in Medicare Part D channel, if you take a look at growth from 2024 versus 2023, it's roughly a 50% growth just in the Medicare Part D channel where it's completely outperforming your Medicaid and your commercial channel, I think they're in single digits. Even growth Q1 2025 versus 2024, it's at 41% growth. There is robust growth, I would say, for Rixulti in Medicare Part D channel. Presumably, that's the ADA indication, even with the black box warning. From that perspective, we're seeing that growth with Rixulti. From a market access standpoint, with it being under the brand name Auvelity, we would anticipate that we would have access out of the gate in the Medicare Part D channel. By having an sNDA and using the brand name Auvelity, we would anticipate that we would have coverage out of the gate in Medicare Part D. We would anticipate that to be roughly 70% of the total scripts. Yeah. Maybe to layer on to that a bit, we touched on this a little bit with the current commercial infrastructure and account managers. There's overlap now with some of the targets and growing that in terms of any type of realignment or retargeting that would need to be done. That work is underway now. Even if one would want to complement the current team with additional focusing. For example, we are not currently targeting in long-term care facilities and things like that. That's something that's being assessed right now if that's something one would want to do with the potential approval. Yeah, there's dramatic unmet need. There's now one approved product that's growing, as Nick mentioned, of certain key differences in the product profile that we think could offer a compelling framework for Auvelity. We'll see. We're excited about the opportunity to work. In terms of the market and some of the segmentational considerations, I know in the past, you guys have talked about wanting to maybe get the patient before they get to the nursing home, right? When they get to the nursing home, my understanding, at least in talking to some doctors, is perhaps the coverage shifts to Medicaid in the nursing home. There are some capitated payment models that maybe make it more challenging to absorb the cost of a proprietary brand medicine. How meaningful is that as a proportion of the market? Do you have a sense of that? Sometimes we can get a little bit of sample bias in the doctor calls that we do. Do you have numbers? I mean, I'm sure the team does. I don't have them handy, but there are considerations with respect to long-term care facilities. There are initiatives in place to monitor and change the incentive for prescriptions of antipsychotic utilization in elderly patients with dementia. There is a star rating and things like that. Obviously, Auvelity is a distinct mechanism of action. There are structural considerations that are distinct that I know that's adjacent to your question, but I think it's informative and potentially interesting. The basis of the question, I think, is correct is that agitation is really a key symptom that leads to placement in long-term care facilities. If you are able to interrupt that, that is for patients, for their caregivers, for their loved ones, that's a huge area of unmet need. That's great. Then also individuals in long-term care facilities, additional treatment options for them, that's important too. Yeah. Maybe just double-clicking on what our data is showing is that, like I said, 70%, roughly 70%, maybe even a little bit more of that is Medicare, of which 25% of the patients in Medicare are LIS patients, which make up roughly 75% of a lot of the scripts. As a reminder, LIS patients really pay nothing out of pocket. We feel that it will be able to, we'll be able to get the product to patients without the issue that we're seeing that came about with MDD with the copay and having that obviously can't do copay in government channels. From that perspective, we feel LIS patients will be able to get the product. The non-LIS patients, you have the cap and smooth provision of $2,000. That also should be a tailwind or supportive of patients being able to smooth out or budget their spend on an annual basis. Okay. Maybe shifting gears to SYMBRAVO, the launch for migraine, where you're at in terms of the launch readiness. I believe you'll be launching that product pretty soon. Remind us, where are you in terms of peak sales for SYMBRAVO migraine relative to Auvelity MDD? $500 million-$1 billion is for SYMBRAVO. For MDD, we have peak sales of $1 billion-$3 billion. For ADA, it's $1.5 billion-$3 billion. Launch for SYMBRAVO, that's targeted for June or slated for June. That's on track. We're excited for that. The preparation's well underway. The field force, they're hired. They're going through training now. They're on board. It's basically final steps before product is in channel and the field force is engaging with HCP. It's an exciting time for us. That's obviously the second product that we've developed internally that we've obtained approval for and will be launching. It's a pretty exciting time. We're looking forward to it, especially because based on the clinical data we generated, highly differentiated in terms of efficacy for patients, which still remains the overwhelming need in the market. In terms of maybe the more conservative outlook relative to, say, MDD, both big markets, right? Is it you feel like the level of genericization or maybe shorter use scripts? What are some of the factors that maybe would drive a more conservative peak number for migraine versus MDD? Oh, yeah. The nature of prescribing product utilization is much different, right? It's chronic intermittent in migraine. And so with depression, whereas, right, that's chronic for the duration of a major depressive episode. So migraine, you have that distinction, right? And so what does that translate into? That translates into a different type of refill number and frequency. Just the current treatment landscape is much different, right? You have two, well, you have a few recent branded launches. So that's, and the dust is kind of settling, or maybe it's better to say it's the framework prior to the SYMBRAVO launch has started to crystallize with respect to that. So there's that. WAC prices and rebating dynamics are distinct across the categories. I think that's another element. Anything you'd add to that? I don't think so. Okay. And where do you see SYMBRAVO kind of finding its positioning within the space? Is it sort of a post-CGRP drug? Do you think you can compete with CGRP, sort of the post-triptan treatment option for doctors who maybe have explored triptans to the fullest and are now migrating to different therapeutic options? The feedback that we're receiving from clinicians based on the clinical data and the profile and the label is that the clinical data, it's very interesting, very compelling because of the types of patient profiles that the registration trials and other efficacy trials that we've run were done in. The feedback from KOLs is that they can actually see it being used in a variety of patient profiles, say, post a triptan or post an oral CGRP. Earlier this year, we read out the Emerge-based retrial, which was in inadequate responders to oral CGRP therapy and compelling data there. What's great is the product, the efficacy of the product, the responses that we saw clinically, it's across patient profiles. A key consideration will be access dynamics. In our mind, the product can offer benefit to patients and HCPs in a number of different niches is maybe the wrong word, but in a number of different patient profiles. It will be the confluence of access, clinician experience, patient outcomes. We will start to see that and have those data very soon. Migraine's pretty heavily on the commercial insurance, I believe, right? When we looked at other drugs, I guess, that have that sort of channel mix, there's a lot of, I guess, subsidized free drug in the early days, right, to get physicians using the product. As investors think about early days, launch ramp and revenue recognition, is that something you'd caution folks that perhaps there could be a high growth scenario as there's sort of a lot of subsidized drug in the early days? I think what you saw from Nurtec and Ubrelvy, there were GTNs in north of 70-80%, somewhere in that vicinity. We don't anticipate that we're going to have as ubiquitous of a free drug program. We are focused on headache centers and major KOLs out of the gate. I think from that perspective, we're going to be mindful of GTN, but we also want to ensure that product does get to patients and that the KOLs are able to write the product and see the patient utilization and see how efficacious the product is. Yeah. Definitely the tad on to what Nick said is the it's a very distinct from, say, depression, right? Depression, that's still heavy in the commercial channel, right? Even so, the categories are different with respect to gross to nets and sampling and helping patients obtain therapy. A lot of it just has to do with market access dynamics. Yep. Maybe what I'll share is that we feel like we're in a much better spot than in 2022 when we launched Auvelity. Now we have two products that the payers are aware of. We have an experienced payer access, market access team that has good contacts, good networks with teams. We've been having, I would say, quality conversations with the payers this time. Okay. AXS-12 for Narcolepsy, just remind us where you're at in terms of gating items to the submission. Have you had your pre-NDA meeting with regulators and kind of where you stand on the single study being, I guess, the sufficient basis for the filing? Sure. We have gotten to a filing this year. We have said second half. More to come, more to come with respect to pre-NDA engagements with the FDA prior to a submission. The efficacy packages, we actually have three studies now that everything is said and done. There was an early Phase II, that is the CONCERT trial. Just over a year ago, we had the results from the SYMPHONY Phase III. Towards the end of last year, we had results from ENCORE, which was another Phase III trial we conducted. We are really pleased with the package that we have and that we will be submitting. That work is underway. I think maybe a couple more, it would not surprise me if we have additional updates in terms of, say, tightening of potential submission expectations, as I mentioned, things like that. Is it fair to think about this as going after the install base of generic venlafaxine? Do you see a broader role? How do you envision launching basically, I guess, in parallel with Takeda's orexin receptor 2 agonist, given presumably their Phase III data mid-summer looks like their Phase II, I think they're on a good track to get approved as well. Yeah. No. Launch dynamics, commercial infrastructure, that's already in place. We have a sleep field force already, and they're detailing Sunosi right now. It's there, and that would be very easy to add a product to that bag and to leverage that infrastructure. We feel really good about that, exactly how it might fit with other entrants and other potentially contemporaneous entrants. That's okay. It's difficult to, I mean, we're fine if that dynamic is playing out. We've seen other cases where actually that increases HCP awareness, attention, which is a good thing. Exactly how that would work, though, I think it's a little difficult to comment on without label. When you step back and say, "What's the clinical data we've generated so far?" focus and indication would be Cataplexy. We have additional other considerations of the product profile, daytime dosing, likely distinct scheduling, right, from what's currently available. We also had other efficacy measures on sleepiness, cognition, etc. Again, it's difficult to know how that might manifest on a label and then how one might position versus other new entrants. We feel very good about the totality of data we have and the product profile itself. All right. We're out of time. So gentlemen, thanks so much for joining us. Thanks for having us. Thanks so much. Thanks. Appreciate it.