Good morning and welcome to the Axsome Therapeutics conference call. Currently, all participants are in a listen-only mode. Later, there will be a question-and-answer session, and instructions will follow at that time. If anyone needs operator assistance during the event, please press star zero on your telephone keypad. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, Chief Operating Officer at Axsome Therapeutics. Thank you. Please go ahead. Thank you, Operator. Good morning, and thank you all for joining us on today's conference call to discuss the approval of Symbravo for the acute treatment of migraine with or without aura in adults. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our investigational agents, our clinical and nonclinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development plans, commercial plans, and possible intended use of cash and investments. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today from the Axsome team are Dr. Herriot Tabuteau, Chief Executive Officer, Ari Maizel, Chief Commercial Officer, Hunter Murdock, General Counsel, and Nick Pizzie, Chief Financial Officer. Also joining on the call today is one of the leading experts on migraine, Dr. Stewart Tepper, Professor of Neurology at the Geisel School of Medicine at Dartmouth and Vice President of the New England Institute for Neurology and Headache. Herriot will first make some opening remarks. Ari will provide an overview of our commercial plans. Dr. Tepper will provide an overview of migraine treatment needs and will then discuss the profile of Symbravo. We will then open the line for questions, and questions will be taken in the order they are received. And with that, I'm pleased to turn the call over to Herriot. Thank you, Mark. Good morning, everyone. Slide six. Yesterday afternoon, we announced that the FDA has approved Symbravo for the acute treatment of migraine. We are pleased that this approval came early, one day prior to the PDUFA goal date. Symbravo is a novel, multi-mechanistic approach to treating migraine that targets multiple pathways underlying a migraine attack. Symbravo can rapidly eliminate migraine pain and return patients to normal functioning with efficacy that is sustained through 24 and 48 hours after only a single dose. Symbravo is engineered with Axsome's patented MoSEIC, or Molecular Solubility Enhanced Inclusion Complex technology, which increases the rate of absorption of meloxicam, enabling its use as a new molecular entity for the acute treatment of migraine. More than 70% of patients experience an inadequate response to current oral acute treatments. Based on its demonstrated efficacy, Symbravo has the potential to address this unmet medical need. The Axsome team is proud to deliver this important new treatment to the estimated 39 million patients living with migraine in the U.S. Next slide. We are pleased with the broad label for Symbravo. The label highlights are shown on this slide. Symbravo is indicated for the acute treatment of migraine with and without aura in adults. In the controlled trials, Symbravo was very well tolerated, with the only adverse reactions with an incidence of 1% or more being somnolence and dizziness, which were reported each in 2% of treated patients compared to 1% for placebo. Next slide. Symbravo was evaluated in two pivotal phase III controlled trials: the INTERCEPT trial, which treated patients when the initial pain was mild, and the MOMENTUM trial, which treated patients when the migraine pain was of moderate and severe intensity. The efficacy of Symbravo was therefore demonstrated across a broad range of settings, including at the earliest onset when the pain was mild, in patients with moderate and severe migraine pain, and in those with a history of various responses to prior acute treatments. Next slide. Both the MOMENTUM and INTERCEPT trials met their co-primary endpoints. In both studies, patients receiving Symbravo rapidly and significantly achieved pain freedom and freedom from the most bothersome symptom two hours after dosing compared to placebo. In the MOMENTUM trial, three times as many patients treated with Symbravo achieved two-hour pain freedom compared to placebo, and in the INTERCEPT trial, twice as many patients achieved pain freedom at two hours compared to placebo. Freedom from the most bothersome symptom, phonophobia, photophobia, or nausea at two hours, was achieved by approximately 40% of patients treated with Symbravo. Next slide. The benefits of pain freedom were sustained through 24 hours, as shown on this slide. 24-hour sustained pain freedom was achieved by three times as many patients treated with Symbravo in the MOMENTUM trial and twice as many patients treated with Symbravo in the INTERCEPT trial compared to placebo. In a head-to-head comparison, Symbravo also significantly demonstrated superiority compared to rizatriptan on sustained pain freedom. Results were similar for sustained pain freedom through 48 hours. Next slide. Notably, the demonstrated efficacy was achieved with only a single dose of Symbravo. Importantly, 85% of patients treated with Symbravo in the INTERCEPT trial and 77% of patients treated with Symbravo in the MOMENTUM trial did not require rescue medication within 24 hours. These results demonstrate that the vast majority of patients achieved significant benefit with just a single dose of Symbravo. Overall, these results demonstrate that Symbravo can rapidly eliminate migraine pain across a broad range of migraine severity, allowing patients to quickly return to normal functioning with efficacy that is sustained through 24 and 48 hours after a single dose. Symbravo is protected by a robust patent estate extending out to at least 2040. With that, I would like to turn it over to Ari, who will review the commercial opportunity for Symbravo in our launch plans. Thank you, Herriot, and good morning, everyone. On the next slide, you see that Symbravo is entering a migraine market in which significant unmet treatment needs exist among patients and providers. Even with multiple approved medications available, more than 80% of migraine patients discontinue their acute migraine treatment in the first year. Migraine remains the leading cause of disability among neurological disorders for the more than 39 million migraine sufferers in the U.S., and the devastating consequences of recurrent, pulsating, severe, and disabling head pain leave patients in constant search of therapeutic relief. Unfortunately, patient dissatisfaction is extremely high in this market due to limited efficacy response or burdensome side effects associated with existing treatment options. These dynamics present a clear opportunity for a product like Symbravo to offer hope to the millions of patients in search of a new treatment approach. Next slide. Looking closer at the market opportunity, there's a large base of over 22 million prescriptions written annually, dominated by generic triptans that make up three-fourths of total prescriptions. Market penetration of newer agents over the past five years reinforces the potential for a novel, multi-mechanistic medicine like Symbravo to create a meaningful impact on the overall acute migraine market by offering the potential for improved patient outcomes. Importantly, the provider audience is highly concentrated among high-decile prescribers in headache centers and large neurology practices, which will enable a targeted salesforce effort for Symbravo during our commercial launch. Next slide. As we prepare for market entry, we've been very pleased with the response to Symbravo's compelling clinical profile, with future HCP targets highlighting Symbravo's rapid and durable efficacy, novel mechanistic approach that targets the four key pathways underlying a migraine attack, and well-established safety and tolerability profile. Three out of every four providers we engaged in market research expect to use Symbravo as an acute migraine treatment for their patients. Next slide. We are planning to launch Symbravo commercially in approximately four months. At Axsome, we believe in taking a strategic and focused approach to commercializing our products, and for Symbravo, that will include a targeted selling effort that prioritizes headache centers and headache specialists who care for the vast majority of migraine patients in the U.S. In addition, Symbravo will be Axsome's third product to leverage our digital-centric commercialization platform, enabling us to engage with providers across the migraine universe in a highly targeted and efficient way. Patient education will also be an important part of our promotional mix, with unprecedented digital and traditional media channels available to educate patients throughout their migraine treatment journey. Finally, we are actively engaged with payers across channels to educate on Symbravo's unique value proposition in anticipation of securing access for the product in its launch year. We will share more details around our commercialization plan soon. Next slide. I'd now like to hand the call over to Dr. Stewart Tepper, Professor of Neurology at the Geisel School of Medicine at Dartmouth and Vice President at the New England Institute for Neurology and Headache. Please go ahead, Dr. Tepper. Thank you very much. It's really a great honor to be able to talk about the acute treatment of migraine and the advent of Symbravo. What I want to do is sketch for you how we got here in terms of the understanding of migraine, some specific aspects of Symbravo. I was one of the investigators in these studies, and then where this might fit in from a clinical standpoint. Next slide, please. This slide takes you through what we know now about migraine pain and the genesis of migraine. Migraine pain is actually a non-infectious meningitis. That's why it hurts so much. If one begins at the upper left in this set of diagrams, migraine itself begins in the brain and then activates the mechanisms of pain in the meninges. Activation of the migraine within the brain leads to CGRP release in the meninges. In the second frame at the top, the CGRP is released in the meninges during the migraine. In the upper right, what happens is two major events. Blood vessels dilate because of the CGRP effect. CGRP is a profound blood vessel dilator. When the blood vessels dilate, they open up and outpour the mediators of inflammation. You can see on the lower left the inflammation occurring. This is typical inflammation. In the second frame at the bottom, one sees the actual migraine pain mechanisms, which are caused by the blood vessels dilating and the inflammation in the meninges. That hurts. Signal goes back into the brain and it's processed. The pain signals are processed in the brain. That's when people perceive the pain, when they get nausea and sensitivity to light and noise. One way to approach this, of course, is to take out CGRP, but there are lots of opportunities for reversing migraine pain that are afforded by coming in from different mechanisms. Next slide, please. Symbravo combines MoSEIC meloxicam and rizatriptan for the acute treatment of migraine. So let's take this apart. Rizatriptan prevents the CGRP release in the meninges. At the very beginning, it prevents the CGRP release. Then it reverses the blood vessel dilation in the meninges, second mechanism. Then it prevents the pain signal from moving from the meninges back to the brain. The meloxicam terminates inflammation in the meninges as a non-steroidal anti-inflammatory, and non-steroidal anti-inflammatories have also been shown to reverse the central processing of the migraine pain. Non-steroidals work both peripherally in the meninges and centrally to stop the migraine. What Symbravo combines is a new formulation of the meloxicam, MoSEIC meloxicam, to increase the speed of onset and the overall effectiveness. On the right, you see this MoSEIC delivery technology, which enhances solubility and absorption. Regular old meloxicam takes a very long time to be absorbed. It's really more appropriate for preventive effects in various kinds of arthritis. It's a molecule with low solubility and poor absorption. But with this new formulation, there's a pH modifier, there's a drug inclusion complex formulation, and this improves the drug release and enhances the absorption. So on the one hand, you have this new MoSEIC meloxicam at a different dose than generic meloxicam to maximize the onset. And then rizatriptan actually is the triptan, the oral triptan with the fastest onset and the highest two-hour pain-free numbers, which is further enhanced by MoSEIC technology. With the combination of the MoSEIC meloxicam and rizatriptan in one tablet, the whole is greater than the sum of the parts. The FDA, in one of the regulatory trials, MOMENTUM required that the Symbravo be tested against the individual components as well as placebo. Next slide, please. This is a slide of the pharmacokinetics of the drug, superimposed on what actually happens during migraine. If one follows across a migraine, at the bottom you see the time in hours. CGRP peaks at about one hour, and prostaglandin E2, which is an inflammatory mediator, peaks at about two hours. In gold, you see what happens with the Symbravo rizatriptan. It peaks in about 30 minutes, and the MoSEIC meloxicam peaks at between 45 minutes and one hour. The combination of the two medications combined in the medicine all peak before the CGRP and the PGE2, and that enables the drug to terminate the attack so effectively. Remember, with the rizatriptan kicking in early, it's also preventing the release of the CGRP. These components align with the increase in the key mediators of migraine. The pharmacokinetics here actually predicts the clinical effectiveness of this combination medication. Next slide, please. Now, a word about optimal acute treatment in migraine. When we teach, we really focus on getting an optimal acute treatment for patients. The best acute treatment for migraine is one and done. Patient is pain-free within two hours without significant side effects, and most of the time without any headache recurrence after the successful treatment. One and done. There is a large prospective population-based study by Richard Lipton's group, which was able to show over several years in thousands of patients that inadequate acute treatment effectiveness was associated with an increased risk of transforming to chronic migraine over the course of a year. Let me explain that. What was done was to evaluate the acute treatment effectiveness in people who had discrete episodes of migraine and then see what percentage of them actually got worse and got a higher frequency of migraine, greater severity of migraine, transformed to greater than 15 headache days per month. It turned out that optimal acute treatment was more than twice as likely to not be associated with this transformation. Inadequate acute treatment was more than twice as likely to be associated with this adverse event of the natural history going from episodic to chronic migraine. This enabled us to tell each other and patients that we want treatment that gives a sustained and complete response in order to prevent the onset of chronic migraine and medication overuse headache. And the advantage of the Symbravo is that it combines the peripheral and central effects of meloxicam on the one hand with the blood vessel effects and some of the neuronal effects of the rizatriptan on the other hand to offer the prospect of a complete response. I showed you why it should have early onset, why it should have optimal efficacy. It has very low adverse events. You can see that the adverse events that were recorded were only 1% over placebo. Very low recurrence, sustained response, and sustained pain freedom were documented at 24 and 48 hours. So the pivotal trials were very encouraging. Remember also that Symbravo was studied in one of the regulatory trials, MOMENTUM, on those for whom patients had had a lack of success with previous acute medicines. These were more difficult to treat patients, and Symbravo showed excellent results in these harder-to-treat patients. What we really want to do, and this we hope is the future, is to match patient need to treatment for the acute treatment of migraine. That matching of patient need to appropriate treatment is referred to as stratified care. Next slide, please. Stratified care is actually going worldwide. The American Headache Society consensus statement states that individualizing acute treatment plans should be based on medical need and treatment history. Across the world, position statements and consensus statements confirm the idea of matching patient need to treatment. I put the UAE consensus statement there, the Polish experts' consensus statement, which says that we should be considering migraine-specific treatments as first-line therapies. So the future for acute therapy of migraine is migraine-specific acute treatment that focuses on multiple mechanisms of action to achieve a complete response. Symbravo, by combining MoSEIC meloxicam with rizatriptan, allows for additive benefit for patients. And that's why we've been quite excited in the development of this particular medication. I thank you. Thank you very much, Dr. Tepper, and at this point, we'd like to open the call for questions, and to do that, I'll turn it over to the operator to manage the line. Thank you. Thank you. Ladies and gentlemen, the floor is now open for questions. If you would like to ask a question, please press star one on your telephone keypad at this time. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up the handset before pressing the star keys. We do ask that you please limit yourself to one question and one follow-up. Again, that is star one to register a question at this time. Today's first question is coming from Leonid Timashev of RBC. Please go ahead. Hi guys. Congratulations on the approval. Really exciting to see. I had a question on sort of the market and at one point in a patient's treatment journey, you're going to intervene and try to get them on Symbravo. You talked about the high willingness to prescribe as well as sort of the failure of patients to respond to treatment. But what's the churn like in the market? At what point would a patient or a physician consider switching therapies? You do have a broad label, so would you try to use this upfront after they failed some other prior therapy? Yeah, that's it. Thank you. Yeah. So I'll answer part of it. And Dr. Tepper would love to hear your thoughts just about intervention with an inadequate response. But from our perspective, we see Symbravo as being a great treatment option when a patient is in need of a prescription treatment. And whether that is as an initially diagnosed migraine patient or somebody who has tried one or more existing agents and had either inadequate efficacy or intolerable response to treatment, Symbravo will be a great option. And obviously, market access will be an important factor here. We'll have more to share about that as we get closer to the commercial launch. But Dr. Tepper, any thoughts from you in terms of when you think about switching a patient or initiating pharmaceutical intervention for migraine? The first point I think is that it's the position of the American Headache Society that everyone with migraine needs an acute treatment, so we're starting on that premise. I think it's also useful to look at which kinds of patients are appropriate for Symbravo without regard to what the payers are going to require, then circle back, and the fact that the non-steroidal anti-inflammatory can reverse central sensitization requires us to look for patients that are at the peak of their migraine where this kind of a medication could reverse it and where a triptan alone or where a gepant alone might not, and one example of that that's really common is migraine upon awakening, that is morning migraine, and almost half of attacks occur in the morning, and triptans don't really get people back to functioning in morning migraine, and gepants are a bit slow. And so I think Symbravo is going to be very useful in patients who awaken with a full-blown attack. Because of the speed of the rizatriptan and the MoSEIC meloxicam, it also can be useful in patients who have a quick time to peak intensity from the time they notice the pain to the time they're disabled is rapid. And again, gepants tend to be kind of slow, and this medication should be excellent for that. It also should be used in people who have a need for an anti-inflammatory. And I was thinking about menstrual migraine, which occurs in two-thirds of women with migraine. So it's a huge number of patients. And using a medication that combines an anti-inflammatory with a triptan should prolong the benefit. Menstrual migraines tend to be long. Various anti-inflammatories have been shown to be useful in menstrual pain. And so there's an overlap there as well as this reversal of central sensitization. Since the payers are likely to require previous trials, the momentum study, which evaluated patients who had various inadequate responses to acute treatment in the past, shows that this medicine works. And the late Ninan Mathew published a paper on combining triptan plus NSAID in people who had had a lack of success with triptans. And interestingly, when one combines the NSAID with the triptan, it usually works in people for whom the triptan alone has failed. So I think we have a lot of clinical circumstances in which this combination will be useful. Thank you, Dr. Tepper, and we can go to the next question. Perfect. Our next question is coming from Charles Duncan of Cantor Fitzgerald. Please go ahead. Super. Thank you, Herriot and team. Congratulations on the approval. Dr. Tepper, great to hear your voice and reconnect. I had a question for you, Dr. Tepper, and that is probably related to the last question. It seems like you appreciate some of the synergies in the mechanism of action. But do you think that prescribers, KOLs, and certainly general prescribers will see this as just another triptan, or will they appreciate some of the synergies and mechanism? You mentioned stratified care. I guess I'm wondering if you would place this before or after the oral anti-CGRPs, and what is the evidence you'd base that on? Thank you. I'm trying to remember the first question, but let me deal with the second question first, and then you can remind me. I think individualizing acute treatment and matching patient need to treatment or matching the treatment to patient need is really the key. There are going to be people for whom gepants are appropriate. They have low AEs, similar to Symbravo, and they're gentle. And ubrogepant has been shown to be effective in prodrome. So they have some interesting utility. And the more frequent that somebody uses a gepant, the more likely they are to get prevention. So they have some rather unique properties. But there are circumstances in which gepants may not be appropriate. I mentioned a few of them: central sensitization, morning migraine, quick time to peak intensity with a lack of warning that a headache is coming in, or a person for whom the gepant has been inadequate. So I think sitting as a prescriber, there are going to be people for whom the combination therapy is appropriate from the get-go, assuming payers allow it, and others for whom gepants or triptans will be appropriate from the beginning. I do remember your first question, which was, how are we going to educate our compatriots that this is not just another triptan? That's really up to those of us who are teaching to explain that combining multiple mechanisms does afford increased effectiveness. We know that the combination is superior to the individual components as well as placebo. And we have those data, and it's our responsibility to teach our colleagues that this is not another triptan. This represents an advance. Very helpful. And if I may, just one quick follow-up for the company. I guess I'm wondering when you might pursue beyond adults. So for example, to include adolescents, given some of Dr. Tepper's prior comments with regard to menstrual migraine, that might be of use. And then what would you anticipate, or when is the data coming from the post-CGRP trial that's being run? I think that's later on this year. Could you provide additional color there? Thanks. Hey, Charles. This is Mark. So the work for the adolescent work is underway, and we'll have more to say there. And with respect to the EMERGE trial, we anticipate results this quarter. I want to just chime in on this. I want to chime in on the adolescent part of this. One of the characteristics of adolescent migraine is quick time to peak intensity. When one asks an adolescent, "How fast did that migraine get bad?" they say, "That fast," just snap the fingers and so rizatriptan is actually already FDA approved for acute treatment of migraine in adolescents. Since the combination with the MoSEIC formulation moves the rizatriptan and meloxicam even earlier in the pharmacokinetics, as you point out, this is a medication that could be very effective in adolescents. I look forward to seeing the results of that study. As well. Thank you. Thank you. The next question is coming from Ash Verma of UBS. Please go ahead. Hi. Thanks for taking my question. Congrats on the approval here. I guess I wanted to get a sense of what do you see broadly as the peak commercial opportunity here. I mean, in migraine, there's definitely a strong precedent for drugs reaching several billion dollars peak sales type opportunity. So as you look at it sort of early in the launch here, what is your expectation? Could this be a blockbuster? Could it go beyond that? Just would love to hear any thoughts that you have on that. Thanks. Sure. Thanks, Ash. We are very optimistic about the potential for Symbravo. In our current corporate presentation, we have a peak sales range of $500 million to $1 billion. We firmly believe that that range is achievable. But obviously, there's a lot to learn as we get out into the market and see the ramp of the product over time. But that said, we are very optimistic and do believe that Symbravo has blockbuster potential and will look forward to educating the marketplace in a few months. Great. Thank you. Thank you. The next question is coming from Ami Fadia of Needham & Company. Please go ahead. Thank you. Maybe my first question is for Dr. Tepper. You mentioned that there's going to be need for education kind of in the broader physician community. Outside of that, how do you see the utilization of the drug, assuming that payers will require patients to have failed at least one other treatment? How often do you see the patients churning and maybe kind of talk about sort of just receptivity of physicians to kind of try newer products? Thank you. And then just for the company, from a sort of payer strategy perspective and maybe a launch curve perspective, could you give us kind of some initial thoughts around where do you see the product placed with payers, and then what could be a good analog for us to think about for the launch? Thank you. Very briefly, I think that when physicians or providers ask patients about whether they're getting a one-and-done response with tolerability and whether they can use a medication when they need it during the day, for example, at work, and be restored to normal function, when practitioners ask that question, the number of patients that have inadequate response to particular treatments turns out to be remarkably high. And persistence data in multiple studies on triptan use is very low. It's extremely rare for patients to remain persistent with single triptan therapies. So I think there's the prospect of improvement in patient care with this combination medication. And I'll turn it over to the company. Yeah, thanks. And hi, Ami. This is Ari. To answer your questions, from a market access standpoint, we're obviously in active negotiations right now. And we recognize when products enter the market for the very first time, there's going to be different appetites in terms of utilization management or unrestricted access for new products. And so we recognize that not every payer is going to necessarily treat the negotiation in the same way. That said, we're discussing a variety of different access approaches. It could be as first line. It could be with one or two prior treatment failures. And so we're going to be open-minded because we recognize this is a long-term play in terms of the growth of the brand and profitability of the brand. And so we'll have more to share with that as we get closer to the commercial launch. I think in terms of launch curve analogs, obviously, the nearest launches in this space are the oral CGRPs. So I think those are fair comparators. However, there are some meaningful differences. Obviously, those products were launched by larger companies with larger initial sales force footprints, which we recognize. But that said, we're very optimistic about our ability to grow demand in this space. And we'll look forward to sharing more details around those plans as we get closer to the commercial launch. Thank you. Due to the interest in today's topic, we are asking the additional callers to please limit themselves to one question. The next question is coming from Marc Goodman of Leerink Partners. Please go ahead. Hi, good morning. This is Basma, analyst for Marc Goodman. Thank you for taking our question. We'd like to know if there's any plan to go after prevention as an additional indication from Symbravo, as this may help with the uptake, and then if there's time, we have a follow-up question for Dr. Tepper. Thank you. So we'll take that question. So Symbravo is approved for the acute treatment of migraine, so it is not approved for prevention of migraine. Having said that, and maybe Dr. Tepper could comment on this, one of the important aspects of Symbravo we feel is making sure that patients are adequately treated in order to prevent chronification of migraine. Dr. Tepper? Yeah, I think I would think about this as an optimal acute treatment and probably not one suitable for prophylaxis. Thank you. The next question is coming from Joon Lee of Truist Securities. Please go ahead. Hey, congrats on the approval, and thanks for taking our questions. Dr. Tepper, it was really interesting to hear you describe migraine as a non-infectious meningitis with activation of the inflammatory pathway. With uncontrolled or under-controlled migraine, have some lasting damages to the meninges and/or worsened subsequent migraines? And if so, how critical is it to rapidly abort migraine pain? And would Symbravo play a role there? And a quick follow-up for management. Have you disclosed the pricing of Symbravo? Thank you. I don't think the issue is damage in the meninges. There are people for whom migraine becomes a progressive disease. That is, they gradually increase the frequency of their attacks and transform from episodic migraine, having less than 15 headache days per month, to chronic migraine, having 15 or more days per month, and then gradually, and they can actually progress all the way to continuous headache. And we have lots of chronic migraine people with continuous headache. And that progression is linked to inadequate acute treatment and to the frequency of headache days per month. So if you have an optimal acute treatment, let's say you have a person who has a three-day migraine, and they take a medicine one and done, and instead of a three-day migraine, they have a two-hour migraine, they're going from three days of migraine to less than a day of migraine. The likelihood of progressing and transforming to chronic migraine goes down. That's probably why optimal acute treatment is associated with decreased risk of transformation. There are MRI changes that occur in migraine, but these changes are reversible and are not permanent. So we don't think of migraine as a disorder like multiple sclerosis, where there's a gradual increase in lesions and a burden in the brain that develops. Rather, we think about this as a reversible neurologic disorder in which there is the prospect for bad progression and in which optimal acute treatment might prevent that. Hey, Joon. This is Ari. Regarding your question on pricing, we have not disclosed the WAC price at this point, but we'll do so as we get closer to the commercial launch. Thank you. Thank you. The next question is coming from David Amsellem of Piper Sandler. Please go ahead. Thanks. This is a question for Ari. Just wanted to gain more insight into promotion and commercial resources surrounding Symbravo. Can you talk to where the sales force headcount associated with Symbravo is going to be over time? And what is the extent to which your primary care calling effort can synergize with Symbravo in terms of being able to promote Symbravo to GPs? And just given the promotion intensity of the space, what's your view on direct-to-consumer activities? Just trying to better understand the intensity surrounding promotion and sales force resources here. Thanks. Yeah, thanks for the question, David. We recognize it's a highly competitive marketplace. As I mentioned on the call, our intent at launch is to be really targeted and very focused on headache centers and headache specialists, which we think is the most appropriate, most effective way for us to build an initial trial of the product. We also think it's great to be able to educate folks like Dr. Tepper early in the launch so that they can also educate their colleagues across the migraine landscape. Over time, we would expect to analyze and evaluate our sales force size, much like we've done with Auvelity, and when appropriate, expand the team if we believe it makes sense and has high ROI capability. I will say that with the primary care opportunity, there is a high degree of overlap with our Auvelity primary care targets. And so that is something that we'll continue to evaluate in terms of synergies with our sales teams. But that's how we're thinking about it at the moment. In terms of DTC, obviously, this is a heavy consumer activation market as well. No plans to launch DTC right out of the gate, but that's something that we'll also evaluate. And when appropriate, if we feel confident in the base of clinician support and the demand trajectory of the brand, then we may choose to invest in a broader-based DTC down the road. But there will definitely be patient education, but not a full-scale DTC in the way that other products are right now. Thank you. The next question is coming from Jason Gerberry of Bank of America. Please go ahead. Hey, guys. Basic modeling question for me. How should we think about the average scripts per year? Mindful, you haven't launched yet, but I imagine you can extrapolate this off of how patients consume triptans in the acute use setting. And so we had been assuming 5x. I'm wondering if that's kind of the right ballpark number. And if you can firm that up with any good sourcing, I'd appreciate it. Thanks. Yeah, thanks for the question. I think when you look at the market basket, everything from triptans to the oral CGRPs, there is a range of sort of average number of refills in a given year. I think the range, generally speaking, is somewhere between three and five. And so I know that's a fairly broad range. Obviously, we need to get in the market to give more specificity on where we expect Symbravo to land, but I think that gives you a starting point. And a lot of it really depends on how well the patient responds to that specific treatment. As we've talked about a lot on the call, there's a lot of inadequate response, a lot of churn, a lot of switching to new medications. And so it somewhat complicates the average scripts or fills per year. But we feel very confident in the clinical profile of Symbravo, and we feel optimistic about the impact it will have for patients. Good. Thanks, guys. Thank you. The next question is coming from Joseph Thome of TD Cowen. Please go ahead. Hi there. Good morning. Thank you for taking my question and congrats on the approval. Maybe for Dr. Tepper, you did a good job at kind of indicating what patient segments you might particularly be interested in this population. I guess when you look at your acute migraine practice over time, what proportion of your patients do you think will be on Symbravo, or do you think you will like to trial the agent in, assuming that you're able to get reimbursement where you want to use it? Thank you. Yeah, I think the issue is going to be access. It'll be access. That'll be the main issue. If there's access, then the use will be high. And if there's too many, if there are too many obstacles, too many prior approval requirements for documentation, then the access will be lower. And we have opportunity. There's no doubt there's need. I can't give you a percentage because I don't know what the access will be like. Thank you. The next question is coming from Joel Beatty of Baird. Please go ahead. Hi, thanks. Dr. Tepper, maybe a follow-up to the question. Could you describe what you would consider as reasonably good access for this agent that you'd be happy with? What I would think would be good access is no prior approval. And the issue with prior approvals is that when we're required to do it, we're just documenting, and then some person says no because that's the next step, and then we have to appeal, and it's a tremendous lack of productivity. And I think it actually, my theory is that it costs the payers more to do prior approval than to not do prior approval. What I predict is that initially they will require a failure of two triptans in those patients who are appropriate for triptans because triptans are all generic. Do I think that's appropriate? No, because we already know that triptans have very poor persistence. So why bother requiring patients to take medicines that they won't take over time? It's very bad medicine. And also, there's a large group of people for whom triptans would not be the first choice: people with morning migraine, people with menstrual migraine, and so on. So I hate to get up on my soapbox and preach about it, but I think that the prior approvals and the step edits are obstacles that are futile, and the less of them, the better. Thank you. The next question is coming from Graig Suvannavejh of Mizuho Securities. Please go ahead. Great. Thank you. Congrats on the approval, and thank you for taking my question. Questions for Dr. Tepper. Against the backdrop of the category acute treatment being very promotion sensitive, I'm wondering if you could provide a comment on with your practice patients who you feel are very responsive to promotion, the impact of promotion on prescribing patterns, especially against the backdrop of Axsome's statements earlier that at least initially DTC is not being considered. Obviously, they might consider it later, but just trying to get your sense of the impact of promotional activity in the class and prescribing. Thanks. It's actually very interesting. It's a very interesting question, and I have practiced in multiple practice settings: Cleveland Clinic, Dartmouth, now Fairfield County. I almost never have a patient come in and say, "I want the medicine that Lady Gaga takes." I almost never have a patient come in and ask for a particular medicine that's been advertised, and this is in every category of anti-headache therapy: monoclonal antibodies, gepants, in the days of triptans, almost never. Maybe the DTC is working somewhere in primary care somewhere, but boy, I just do not see a clamor for a particular medication based on the advertising on TV. I expect it to, but I really don't, and when I bring up a particular medication that has been advertised, sometimes the patient will say, "Oh, I think I heard about that one on TV." Sometimes not. More often not. I really would say more often not, or they're not telling me anyway. So I can't think of a patient in the last couple of years that requested a drug by brand name. Okay. Thank you very much. Thank you. The next question is coming from Vikram Purohit of Morgan Stanley. Please go ahead. Hi, everyone. This is Morgan. I'm for Vikram. Thanks for taking your question. So I know that pricing hasn't been disclosed yet, but are there any initial thoughts on how you expect gross to net to trend in the early part of the launch and where you would expect this to be at steady state? And then on the sales force, do you have any kind of number around what that particular sales force will look like in the migraine market? Thank you. Sure. Hey, Morgan. This is Nick. Yeah, it's a bit premature to be talking GTN. As you mentioned, we haven't announced or confirmed our WAC as of yet. But I will note that one thing that will differentiate this launch from others is that we do not plan on saturating the market and launch with free goods. We plan to have a more concentrated approach of focusing on top decile headache centers, which will be an important aspect of our payer discussions. And as it relates to sales force, we haven't disclosed the size of the sales force. I think it's fair to look at how we launched Auvelity initially as sort of a guide to how we're thinking about Symbravo. We took a similar approach on being really focused on the psychiatry market with Auvelity at launch. And similarly, we'll be very focused on the neurology headache center market at launch with Symbravo. Thank you. It looks like we have time for two more questions today. Our next question is coming from Myles Minter of William Blair. Please go ahead. Hi. Congrats on the approval. Thanks for taking the question. Question for Dr. Tepper, then one for management to opine on. Just how important is efficacy in the acute timeframe? I think that's defined as within two hours post-dose versus durability of the response at 24 and 48 hours. And then just for management, it appears on the label that the majority of the data is within that two-hour period. So I'm just wondering, considering the data for MOMENTUM that over the 24 and 48-hour period showed a better superiority over rizatriptan, wondering how you can market claims against that data if it's not necessarily included in the label. Thanks very much. I'm not involved in the marketing. I can tell you, though, what patients say. And I've been involved in the genesis of two tools for evaluating the effectiveness of acute treatment based on what patients say. And one of the tools, Migraine- ACT, and another tool, mTOQ, the Migraine Treatment Optimization Questionnaire, validated what patients want. And we evaluated close to 70 different outcome measures to see what it was that patients most wanted in an acute medicine. Number one, by far, both treatment evaluations for acute medicines was pain freedom by two hours. That's what patients want. Everything else, less than that. So sustained effects, important, but less than that. Side effects, important, but less than that. It's pain freedom at two hours that people are seeking. So that's the answer to your question. Yeah. And Myles, regarding your question on the data in the label, that is accurate. However, the FDA does provide very clear guidance on sharing data from clinical trials that's consistent with final label. And so we would expect to be able to share some additional analyses, additional data sets, as long as it's consistent with the FDA's guidance. And so our team is working through that. And we'll have more to share as we finalize the brand story closer to launch. Lovely. Thank you. Our final question today is coming from Serena Chen of Wells Fargo. Please go ahead. Hi. Thanks for taking my question. Wanted to get a better sense of the acute market. How many migraine days per month are these patients having? And is there any reduction in migraine days after medication use? Thanks. I guess that's for me. The majority of patients with migraine have episodic migraine. That is, they have less than 15 headache days per month. The percentage of patients in the population with chronic migraine, 15 or more headache days per month, ranges depending on the population-based study between 2% and 7%. Whereas episodic migraine, the population of people in the U.S. with episodic migraine is at least 12%. That's 12% of the total population. That's a huge number. The majority then of people will have episodic migraine. I hope that answers your question. Great, and thanks, Dr. Tepper. With that, that rounds out the Q&A session, so we'll hand over the call to Herriot for closing comments. Thank you all for joining the call. I especially want to thank Dr. Tepper for his time and his comments and sharing his expertise. We are thrilled to be making Symbravo available to patients with migraine. We would like to also thank the patients and investigators who participated in the clinical trials of Symbravo. The approval of Symbravo and the ongoing commercialization of Auvelity and Sunosi, we will now be commercializing three important new CNS products. In addition, the rest of our pipeline continues to advance with several NDA and pre-NDA stage product candidates, including AXS-14 in fibromyalgia, AXS-05 in Alzheimer's disease agitation, and AXS-12 in narcolepsy. We are committed to discovering, developing, and delivering potentially life-changing medicines to people living with serious CNS conditions. We look forward to updating you on our continued progress in the coming months. Have a great day. Ladies and gentlemen, thank you for your participation. This concludes today's event. You may disconnect your lines or log off the webcast at this time and enjoy the rest of your day.