Study Result

Apr 6, 2020

Good morning, ladies and gentlemen, and welcome to Axsome Therapeutics Conference Call. Currently, all participants are in a listen only mode. We will be facilitating a question and answer session towards the end of today's call and instructions will follow at that time. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mr. Mark Jacobsen, Chief Operating Officer at Axsome Therapeutics. Please go ahead. Thank you, operator. Good morning, everyone, and thank you for joining us on today's conference call to discuss the positive top line results from the INTERCEPT Phase 3 trial of AXS-seven in the early treatment of migraine. A press release announcing that AXS-seven achieved the co primary endpoints in the trial crossed the wire a short time ago and is available on our website at axome.com. 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 non clinical 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 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 Axsome's management team are Doctor. Herriot Tabuteau, Chief Executive Officer Doctor. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs Mr. Nick Pizzi, Chief Financial Officer and Mr. Dave Merrick, Chief Commercial Officer. Herriot will start by providing an overview of today's announcement before turning the call over to Cedric, who will review in greater detail the top line results of the INTERCEPT clinical trial. Following Cedric's presentation, we will open the line for Q and A. Herriot will then close-up the call with some concluding remarks. I shall now turn the call over to Herriot. Thank you, Mark. Good morning, everyone, and thank you all for joining us on the call today. We are extremely pleased to announce that AXS-seven, Axsome's novel, oral, multi mechanistic, investigational medicine for the acute treatment of migraine, not only substantially and significantly eliminated migraine pain, but importantly also substantially and significantly prevented progression of migraine pain in the INTERCEPT Phase 3 trial of AXS-seven in the early treatment of migraine. In the study, AXS-seven met the 2 co primary endpoints of freedom from migraine pain 2 hours after dosing with a p value of 0.002 and freedom from the most bothersome symptom 2 hours after dosing with a p value of 0.003. The percentage of patients achieving migraine pain freedom at 2 hours with AXS-seven, which was 33% in this trial, is among the highest reported for any oral agent in recent studies. The percentage of AXS-seven patients achieving freedom for most bothersome symptom at 2 hours was also substantial at 44%. This trial was designed such that patients were instructed to dose at the earliest onset of migraine pain, while the pain was mild, which represents the anticipated real world use of AXS-seven. The results of this study demonstrate that the rapid absorption in multiple mechanisms of AXS-seven in combination with early treatment significantly prevented the progression or worsening of migraine pain beyond mild intensity. After a single dose of AXS-seven, there was no progression or worsening of migraine pain in 74% of patients compared to 47% of placebo patients over 24 hours with a p value of less than 0.001. The symptom improvement with AXS-seven translated to significant functional benefit with 74% of AXS-seven patients reporting no functional disability at 24 hours compared to 47% of placebo patients with a P value of less than 0.001. The durability and clinical meaningfulness of the effects of AXS-seven are further reflected in the substantially reduced use of rescue medication over 24 hours, which was required in only 15% of AXS-seven patients compared to 43% of placebo patients with a p value of less than 0.001. These lower rates of rescue medication use are notable considering patients were treated with only one dose of AXS-seven. Most pivotal trials of acute migraine treatments require patients to wait until their headache pain intensity is moderate or severe before taking study medication. However, even FDA guidance notes that dosing in this manner is contrary to what is typically recommended by migraine experts. The INTERCEPT study was designed to replicate the anticipated real world use of AXS-seven and therefore these positive results are especially notable because they provide further compelling evidence of the potential of AXS-seven in the acute treatment of migraine. As a reminder, our Phase 3 MOMENTUM study, which reported positive results at the end of last year, was conducted in a difficult to treat patient population with a history of inadequate response to prior acute treatments. These patients were required to wait until their migraine pain was a moderate or severe intensity before dosing. With the INTERCEPT and MOMENTUM Phase 3 trials, AXS-seven has now been evaluated in 2 positive well controlled trials. These studies demonstrate the efficacy of AXS-seven against both a potent active as well as against placebo comparators across a spectrum of migraine attack settings regardless of the timing of migraine treatment, disease severity, prior treatment experience or baseline pain intensity. Our planned NDA filing for AXS-seven in the acute treatment of migraine based on the MOMENTUM trial is strengthened by the Indecept results. Our long term open label trial of AXS-seven in migraine patients, the build safety database required for an NDA filing is on track with more than 700 patients dosed. To date, more than 1800 patients with migraine have been dosed in our completed and ongoing trials. We are on track to file an NDA in the Q4 of this year with the goal of making AXS-seven available to patients as quickly as possible. The rest of our CNS pipeline continues to progress. And in the near term, we remain on track to report top line results from our pivotal advanced Phase twothree trial of AXS-five in Alzheimer's disease agitation in early Q2. The seriousness of migraine is underappreciated. The World Health Organization classifies severe migraine attacks as among the most disabling illnesses comparable to dementia, quadriplegia and active psychosis. Migraine damages family life, social life and employment. The importance of rapid and early treatment of a migraine attack is widely accepted among migraine experts. Suboptimal or prolonged time to treatment has serious consequences as large scale studies show that in addition to the debilitating pain, it can lead to increased progression from episodic migraine to chronic migraine. There is therefore an urgent need for new treatments that provide improved efficacy for the serious neurological disease. AXS-seven is a novel, oral, rapidly absorbed, multi mechanistic investigational medicine for the acute treatment of migraine consisting of mosaic meloxicam and rizatriptan. AXS-seven is thought to act by inhibiting CGRP release, reversing CGRP mediated vasodilation and inhibiting neuroinflammation, pain signal transmission and central sensitization. Axsome's MOSAIC technology significantly increases the speed of absorption of the meloxicam component after oral administration, while maintaining a long plasma half life. AXS-seven is covered by 27 issued U. S. And international patents providing protection out to 2,036 and Axon maintains worldwide rights. I would now like to turn the call over to Cedric, who will review the INTERCEPT top line results in greater detail. Thank you, Herriot. The INTERCEPT or initiating early control of migraine pain and associated symptoms study was a Phase 3 randomized double blind placebo controlled multicenter trial to assess the efficacy and safety of AXS-seven in the acute treatment of migraine. 302 patients were randomized in a one to 1 ratio to either AXS-seven or placebo and were instructed to take a single dose of study medication at the earliest onset of migraine pain when the pain was mild and before it had reached moderate or severe intensity. The co primary endpoints of the study were pain freedom at 2 hours and freedom from the patient's most bothersome migraine associated symptom, nausea, photophobia or phonophobia at 2 hours for AXS-seven as compared to placebo. Secondary endpoints included sustained pain freedom, freedom from pain progression or worsening, improvement in functional disability and the use of rescue medication. Shown here are the key entry criteria. Eligible patients were between 18 65 years of age and required to have an average of 2 to 8 migraine attacks per month. Patients were excluded if they had other headache conditions or significant cardiovascular disease. The demographics of the patients enrolled in the INTERCEPT study are representative of the migraine population. Over 85% of the subjects were female with a mean age of 41 years. There were no meaningful differences in baseline demographics across the treatment groups. All subjects reported mild migraine pain intensity at baseline prior to dosing the study drug as intended by the study design. Now to the efficacy results. On the first co primary endpoint of pain freedom at 2 hours, a statistically significantly greater proportion of patients treated with AXS-seven were pain free as compared to placebo, 32.6% versus 16.3%, respectively, for a placebo adjusted difference of 16.3% with a p value of 0.002. On the 2nd co primary endpoint of freedom from the patient's most bothersome migraine associated symptom, photophobia, phonophobia or nausea, a statistically significantly greater proportion of patients treated with AXS-seven were free of their most bothersome symptom at 2 hours as compared to placebo 43.9% versus 26 point 7 percent respectively for a placebo adjusted difference of 17.3% and a p value of 0.003. AXS-seven provided rapid and substantial freedom from migraine pain as shown on this slide. The percentage of patients achieving pain freedom with AXS-seven was numerically greater than placebo starting at 30 minutes and statistically significant by 90 minutes. Nearly 2 thirds of patients treated with AXS-seven achieved pain freedom by 12 hours. The MOSAIC meloxicam component of AXS-seven has a long half life, which provides the robust sustained efficacy effects seen with AXS-seven. At hour 12, the pain freedom rates were 64% for AXS-seven and 42% for placebo with a p value of less than 0 point 001. At hour 24, the pain freedom rates remained high, 69% for AXS-seven 47 percent for placebo with a p value of less than 0.001. The therapeutic gain of AXS-seven improves over time with placebo adjusted differences in rates of pain freedom greater than 20% starting at hour 4 and for every time point thereafter. Treatment with AXS-seven resulted in statistically significantly greater rates of sustained pain freedom. 22.7% of patients receiving AXS-seven who achieved pain freedom at hour 2 remained pain free at hour 24 compared to 12.6% of those receiving placebo with a p value of 0.03. On the right side of the slide, sustained pain freedom from 2 to 48 hours shows similar results with 20.5% of patients receiving AXS-seven and less than 10% of patients receiving placebo with a p value of 0.013. These results are especially compelling as patients only received a single dose of AXS-seven. Freedom from the patient's most bothersome migraine associated symptom was numerically greater with AXS-seven at all time points measured. Statistically significant improvements were noted at hour 2, the co primary endpoint and at hour 4. Within 4 hours after a dose of AXS-seven, over half of the subjects reported complete resolution of their most bothersome symptom. At baseline, the most common, most bothersome symptoms were photophobia reported in 63% of subjects followed by nausea in 21% of subjects. The ability of early treatment with AXS-seven to prevent progression or worsening of migraine pain was evaluated in the INTERCEPT trial. In the study, patients were instructed to treat their migraine at the earliest onset of migraine pain when their pain intensity was mild. On this slide, we present the pain progression defined as a pain intensity worse than mild or the need for rescue medication. As is shown here, AXS-seven substantially and significantly prevented migraine pain progression beyond mild. AXS-seven prevented progression of migraine in 70 4 percent of treated patients versus 47% for placebo at 24 hours with a p value of less than 0.001. The ability of AXS-seven to prevent pain progression is evidenced by the pattern of use of rescue medication, which is shown on this slide. The percentage of placebo subjects requiring rescue medication increased significantly over time, reflecting worsening pain. In contrast, the use of rescue medication in patients treated with AXS-seven was very low and relatively unchanged over time, reflecting AXS-seven's efficacy in preventing migraine pain progression. 24 hours after a single dose of only 15% of patients require the use of rescue medication compared to 42% of placebo patients with a P value of less than 0.001. The efficacy of AXS-seven in entirely eliminating or halting the progression of migraine pain is beneficial in reversing the disabling symptoms of migraine and allowing a patient to return to normal functioning as described on this slide. As shown here, 74% of patients treated with AXS-seven had no functional disability after 24 hours compared to 47 percent receiving placebo with a p value of less than 0.001. The symptomatic functional benefits of treatment with AXS-seven translated to global improvements in migraine. On this slide, the patient global impression of change at 2 hours was highly statistically significant in favor of AXS-seven. 52% of patients receiving AXS-seven reported very much or much improved 2 hours after the dose as compared to 28% receiving placebo with a p value of less than 0.001. AXS-seven was safe and well tolerated in the study. The most commonly reported adverse events with AXS-seven were somnolence, dizziness and paresthesia. There were no serious adverse events. And overall, the safety profile is consistent with that, which was seen in the MOMENTUM study. In summary, in the INTERCEPT study, treatment with AXS-seven resulted in rapid, sustained and statistically significant efficacy as compared to placebo. Early treatment with AXS-seven resulted in substantial and significant prevention of migraine pain progression, which translated into significantly less use of rescue medication with AXS-seven as compared to placebo and return to normal functioning in the vast majority of treated patients. Finally, AXS-seven was safe and well tolerated in the study. We would like to thank all the patients who volunteered to participate in the INTERCEPT study. We would also like to thank all the clinical site staff who collaborated with Axsome in the execution of this important study. With that, I would like to hand the call back over to Herriot. Thank you, Cedric. I'd like to hand it back to the operator to open the line for questions. Certainly. Charles Duncan with Cantor Fitzgerald. Your line is open. Hey, good morning, Herriot and team. Congratulations on these very good results with AXS-seven. I had a couple of questions, so I appreciate you taking them. The first is regarding, Centric mentioned the reduced function of disability. Can you tell us how that was measured? Thanks, Josh, for the question. I'll hand it over to Cedric. Hey Charles. So yes, so the functional disability scale is one of those scales that asks you whether you have had no change in functional disability, much improved, very much improved or worsened. So and it's asked at a particular time point to assess how the patient regards their level of functional ability. So coming in at baseline, you have a range of disability. And despite, being evaluating mild and early onset, there was quite a great degree of disability at baseline. And then at the 24 hour mark, you asked the patient to what degree they feel that they've improved. And what was compelling about these data was the fact that treating the migraine and getting those high rates of pain freedom at 2 hours, coupled with arresting the progression of the attack translated very proportionally similar into patients at 24 hours saying that they were much or very much improved, 74% with AXS was 7% and 47% were placebo. Okay. And you may have not Hey, Charles. Just to clarify Cedric's response. As Cedric mentioned, we did, of course, ask patients for their level of improvement over time, the global that's the global measure. With regards to the actual functional disability scale, It is the same scale which has been used in other migraine studies. So it's just the exact same scale that has been used by the sponsors. And it actually does look at specifically whether or not somebody can perform normal daily activities or whether they have to stay in bed or whether they're incapacitated. So we do measure that in the exact same way as other migraine studies that you're familiar with. Yes, that's helpful. I figured that it was validated scale. Did you you may have not done this analysis, but did you detect any if so, did you detect any differences in the most in the efficacy in the patients with most bothersome symptoms? I think about 60 well, almost 2 thirds were photophobia versus nausea? So we have yet to look at those analysis, but when you break it out by most bothersome symptoms. But what I can tell you is that 63% had photophobia at baseline and 21% had nausea@baseline. Okay. And then second question was regarding the placebo side of things. I mean, these are very nice data. It looks like the placebo activity in the control arm was relatively good compared to other recent trials. And correct me if I'm wrong if that's not the case, but what would you attribute this to? Is this due to studying patients? I think, Ariel, you mentioned earlier sign of migraine pain or did patients have call it a differentiated in those patients that are experienced with triptan therapy do they have a differentiated experience with AXS-seven? I'll let Cedric comment. But with regards to the placebo response rate, it's along the lines of what one would have expected in this all comers population. So it is higher than what we're seeing in our MOMENTUM trial. But remember, MOMENTUM was in a very refractory patient population. So their placebo response was even lower. But this is along the lines of what we would have expected. It's not much greater than what we would have expected. So you're right that we're able to control the placebo response. And Charles I'm sorry, go ahead. So just Charles, just to say, the triptans are widely regarded as the most effective agents out there for the acute treatment of migraine. So in INTERCEPT, we had 2 hour pain freedom rates that are amongst the highest, if not highest of recent oral entrance. And then you couple that with the results from momentum where we showed CIFI significant superiority over rizatriptan, widely regarded as one of the fastest acting, if not the most potent of triptans. You put all that together and now with INTERCEPTA momentum, the efficacy of AXS-seven has been described in a broad range of clinical settings. So I think that it adds very compelling efficacy data regardless of timing of treatment or baseline illness severity or prior response, right, because inadequate response was characteristic of the patients and momentum. So now you have a broad breadth of efficacy data for 7 in these varied clinical settings? Yes, very nice clinical efficacy. Last question, I think you enrolled 152 that Can you just help us understand, did the 12 other patients just not have migraine? No, actually what happens there is either they didn't dose for whatever reason, they didn't have a migraine or they withdrew consent. So these numbers are what you'd expect to see. Okay. Good deal. Thanks for taking my questions. Congrats. Thank you. Ram Selvaraju with H. C. Wainwright. Your line is open. Hi, thanks very much for taking my questions. Just three quick ones, if I may. With respect to how you expect to position AXS-seven relative to other drugs that are currently approved for migraine, can you give us a sense of specifically how the INTERCEPT data set is likely to aid in that positioning? And also if you expect the INTERCEPT data as strong as it appears to be to have a significant impact on potential formulary positioning? And then secondly, I was wondering if you could comment on the safety profile specifically in relation to another triptan formulation called Qtrypta, which apparently reported very low instances of triptan like side effects in its pivotal program. And just wanted to see if you could provide some additional color on the incidence of specifically triptan like side effects in your INTERCEPT study? Thank you. Sure. Thanks, Ron, for the question. I'll turn it over to Dave to answer your positioning questions. And with regards to the safety profile, we were very pleased with the safety profile. And there as you can see, we had to really, really look for very low cuts in terms of percentage of subjects reporting individual adverse events in order to come up with a table. So very, very low rates of adverse events, placebo like. And in terms of triptan like side effects. We have not seen anything that is out of the ordinary. And also, we are studying AXS-seven in our long term open label safety extension trial and those patients are actually dosing every migraine. And so far, there's nothing unexpected that we're seeing. So we're very pleased with the safety profile. Dave? Hey, good morning, Ram, and thank you for the question. I think when you think about the positioning of AXS-seven, we are in a really good spot. Whenever we think about positioning, we think about what's the unmet need out there. And consistently, we hear that efficacy is what the greatest by far unmet need is in the marketplace. So when you think about what we have to offer with AXS-seven, we asked physicians at the end of last year, 1st based just on the MOMENTUM data, Where would you position this? And what we heard was where there that for patients who had failed multiple therapies, they would prescribe this 40% to 50% felt like this is where they would prescribe it AXS-seven. But they also said they would prescribe it for about 20% of their treatment naive patients. So with momentum, we showed that for treatment experienced patients, this is really a great therapy for you to choose because we're the ones who have data that shows superiority over standard of care in that patient type. So you could first think of experience from treatment experience. Now though, what we've shown is in an all comer patient setting, why wouldn't you move this up earlier? And what we've shown now is if you take the therapy the way that physicians most frequently instruct their patients, 3 out of 4 patients are not going to progress beyond mild. And so we think from a positioning perspective, the positioning of AXS-seven will be really strong and superior efficacy over standard of care in an oral convenient to take oral product with very favorable safety profile. So when you look at that, you would see us being used certainly source of business upfront would largely be the patients are frustrated with and looking for a more effective option, but very clearly could move up to a first line therapy. As far as formulary position, we're also in a very good situation. When you think of the type of data that payers are looking for, head to head superiority data, we think positions us very well for those discussions. In addition, now the data today say that if you take AXS-seven early, not only do you have the ability to not progress beyond mild, but you can return to normal functioning for 3 out of 4 patients. And really important to payers is the cost of rescue medications added to the therapy. So what we saw today was only 15% use of rescue therapy. So that combined that entire clinical profile, we think positions us very, very well with payers to be used early in the treatment of migraine. And then just with respect to the promotional sort of competitive environment, it seems to us anyway that the bulk of the newly approved migraine agents are specifically targeting prevention. And so their promotional message and overall targeting is going to be very different to that with AXS-seven. So could you maybe comment on sort of the kind of promotional headspace bandwidth that you anticipate will be available for AXS-seven as and when it gets to the market? Thanks. Sure. Well, first, I think with, one of the greatest opportunities within migraine is just getting more patients treated and with a sense of urgency to improve the outcomes of these patients. So having more players in the market helps us draw attention to the unmet need, whether that's in the acute space or in the prevention space. And remember, every patient who's on a preventive therapy is also on an acute therapy. And so while there are strides to improve care for preventive therapies, when you look at one of the predictors of progressing from episodic to chronic migraine is insufficient effectiveness in the acute therapies. So we have a very important role to play in terms of making sure that all of the patients who are on therapy, certainly on acute therapies, have the best, most effective option at their hands. And we think that we're in a very good position to be able to address that. And so the focus is on increasing efficacy in acute therapy and anyone who has migraine should have an effective acute therapy in their hands. Gautam Sinija with Guggenheim Partners. Your line is open. Good morning, everyone, and thank you for taking my questions and congrats on good results today. So in terms of similar question or similar lines of question to what Ram asked earlier, just help us understand the label that you are hoping to get because Intracept was more frontline and then you have MOMENTUM, which was more late line. So that's the first question. The second part of the question I have is that it seems like you had excluded patients with cardiovascular disease. So can you maybe put some numbers around what proportion of patient or migraine patients have cardiovascular related disease? And will you be seeking for a counterintelligence for that? Thanks, Jan, for the question. With regards to the label, so the indication that we'll be filing our NDA for is the acute treatment of migraine in adults with or without aura. So that will be the label. And with regards to the role of the momentum in the MICEF trials, we think that both of these studies are will be or are likely to be included in the product label. And so that should inform clinicians in terms of how to use the product. And what's nice is with Momentum and with INTERCEPT, we do have a broad range of patient types and disease severity and ways to treat the migraine. So we do think that that will definitely be useful to have in the label. With regards to the exclusion criteria, that is a standard exclusion criteria. In most clinical trials, you will exclude patients who have very severe underlying disease. And so our exclusion criteria is pretty standard and it's actually used in other migraine studies with other agents of other classes. And with regards to what the implication of that might be for the label, we do expect that the contraindications that are in the label for triptans for with regards to cardiovascular risk factors will be in the label for AXS-seven. In multiple surveys, however, clinicians indicate that roughly it's in the teens, the percentage of patients who would be contraindicated or to whom they do not they would not prescribe and are not prescribing triptan containing products. So in our mindset survey, it was somewhere between 12% 15% and that's been replicated in other surveys of physicians. Got it. Thank you very much. Mark Goodman with SVB Leerink, your line is open. Mark Goodman, your line is open. Sorry, I hear you. Can you give us a sense of what was the number of migraines that these patients had? I know that there was some inclusion criteria you mentioned, but I was wondering what was the actual number that and did you look at the patients to see if they had more migraines, did they respond better and how that was? And were the patients on any background medication, were they allowed to have any other triptans at all? Were they on prevention? Just to make sure of that. Thanks for the question Mark Cedric. Hi, Mark. So, yes, you're right. The inclusion criteria was 2 to 8 on average, 2 to 8 migraines per month. We haven't yet looked at how it breaks down in terms of number of migraines. And the other question were contraindications or sorry, prohibited meds. They weren't allowed to be on other triptans, but there weren't a significant we would have to look at the numbers that were on prevention. I just don't have those numbers right in front of me now. But it was very essentially an all comers population with just the standard contraindications on prohibitions on comorbid conditions, cardiovascular disease, things like that, but otherwise an all comer population. So some of these patients or a lot of these prevention injectable? I don't have those numbers right here with right now. Yes. And if I may add to what Cedric just said, the so the way the study was designed is patients came in and prior to dosing with AXS-seven, there was a 1 month period of time where they recorded their migraines. So in terms of the actual number of attacks that they had during that time period, we do have those data. We just need to analyze them. And while as Cedric mentioned, we don't yet have an exact percentage of patients who were receiving background preventative medications, including the CGRP receptor antagonist. Those were allowed. So that was not an exclusive criteria. So patients could be background preventative medications as long as those doses were stable and as long as they still met the criteria in terms of the number of migraines that they needed to have in order to be treated. And then in terms of other medications, as you know, the way that these studies are designed, obviously, during the first two hours, since 2 hours is the primary endpoint, Patients are not allowed to dose with any kind of rescue medication. And then, I mean, although some do dose a little bit before. But then thereafter, patients are allowed to use rescue medications, so which are the standard rescue medications, which might include triptans. And then just second, in your market research, does it look like the product will be used after a triptan and possibly before CGRPs or equal to CGRPs or how and I'm talking about the oral rescues that were just approved. Just curious what your market research says? Great. So that sounds like a question for Dave. Yes. Well, we did ask the question the where physicians would use AXS-seven. And I think what really differentiates what we're offering is the superiority versus rizatriptan. I mean that makes a significant difference in physicians' minds when they start to think through where they're going to place this product. And so when you think about typically what happens, they typically start with a triptan. More times than not, it does not bring the effective efficacy that they're looking for. And so they wonder, okay, what's the next best step? And so our data that shows superiority over rizatriptan really helps them answer question because we have the data that says for difficult to treat patients, AXS-seven is superior than rizatriptan in that next choice. And so I think the initial use for many physicians will be for those physicians or patients that they're struggling with. But remember, our research also asked the question, would you use this in place or in front of emerging therapies, including oral CGRPs? And remember that 90% of physicians said that they would choose AXS-seven slightly, moderately or significantly greater than CGRPs. And that's because of that differentiated data. So I think that's what is really exciting is they're looking for superiority head to head superiority data And I think that puts us in a very good position relative to new entrants as well as traditional entrants. The final point I would make is that would be for those patients who have already been treatment experienced. But again, I would echo physicians also said that they would prefer AXS-seven for just over 20% of their treatment naive patients. So they're looking at specific types of patients that they think need this type of efficacy right out of the bat from the very beginning. And so we would expect that the MOMENTUM data now coupled with what we see about the ability to prevent the progression of migraine pain could really move us up into first line for a percentage of those patients. Thank you. Thanks. Myles Minter with William Blair. Your line is open. Hi, guys. Good morning and congrats on the data. Just the first one on the patient baseline demographics. I'm curious whether the breakdown of most of the symptoms at baseline in INTERCEPT were similar with momentum. I know Cedric made the comment on the INTERCEPT trial here that 23% had nausea. I don't think I've heard that commentary out of momentum and considering the different patient demographics. So I was just curious as to how those both match up? And I have a follow-up after that. Thanks. Good morning, Myles, and thank you for the question. So we have not done the full exact analysis, but we certainly have those numbers and we would expect that they would be similar. We'll get those precise numbers to you though. Okay. Thanks for that. And then just back on the mindset survey, just curious what the breakdown of survey participants were of primary care providers versus migraine specialists, like your Doctor. Liptons of the world. I'm just thinking that even though 20% might prescribe this in treatment naive patients, whether or not that's going to be your initial sort of sales targeting process considering prior commentary that you'd probably target the specialist centers first and then build out to primary care physicians later? Thanks, Myles. It's Dave. When we looked at the mindset survey, we did ask physicians who were treaters of patients with migraines. So the criteria was to enter the survey was to treat at least 100 patients personally or actively in a 12 month period. Across the 100 participants, they treated about 50,000 patients annually. So it's pretty significant. And the breakdown was around 40% of them were headache specialists, around 35% were neurologists and about 24% were primary care physicians. And so when you look at the bulk of the prescribing, these are the type of physicians that we think represent the bulk of where or disproportionate share of where the patients reside. And so that's why we feel confident in asking these physicians what their distribution would be across treatment naive all the way through treatment experience. So we still feel confident that targeted approach to these types of physicians, those that have a high volume of migraine patients makes sense right from the beginning. But as we move into greater adoption and payer formulary start to kick into place, then we'll have the ability to scale quickly based on the trajectory of adoption. So we think a targeted approach at the very beginning still makes sense, not only to capture the treatment experience, but treatment naive patients and then the ability to scale very quickly. Okay. And then just a final follow-up for me. Just your thoughts on maybe moving from an oral pill into an injectable format or an orally dissolving tablet, maybe even an intranasal formulation given optionality is also an issue for patients out there as well? That's it for me. Thanks. So those are definitely options. And I think certainly one of the things that we are exploring are alternate formulations for the pediatric population. So stay tuned and we'll provide you more information on that later. Thank you. Bert Hazlett with BTIG. Your line is open. Yes. Thanks for taking the question and congratulations on the supportive results. I realize that the current regulatory standard is pain freedom and most bothersome symptom freedom at 2 hours. Did you happen to look at one of the older measures pain relief at 2 hours in this study? Hi, Bert. Thanks for the question. So the way that the study was designed, the study was designed specifically to have patients treat their migraine pain at the earliest onset of migraine while the pain was mild. So we looked at pain freedom, so meaning then you completely eliminated the pain. So in this case, since you're comparing it to baseline, pain relief and pain freedom are identical. Okay. Thank you. And then the measures at 1 hour, given what you saw in momentum, were you kind of surprised you didn't see more of a separation at 1 hour? Not at all. Again, the point of the study was to have patients treat their migraine pain at the earliest sign of migraine pain. And so the point was to actually prevent patients from progressing. And we saw that we demonstrated that very convincingly. So not only were we eliminating pain in a third of patients, but then we prevented pain from progressing from beyond mild. And when you look at all that together, then almost 3 quarters or 75 percent of patients either had their pain totally eliminated or did not progress beyond modest. Now having said that, we still did see numerical separation and numerical superiority starting at 30 minutes. Now when you think about the results of this trial, I think and think about the P values with Cissel significance that we showed, it's important to remember that we dosed a total of 2.83 patients, so we enrolled 302. So that's about 130 or so patients per arm. And to have been able to show the high level of statistical significance that we showed really speaks to the effectiveness of the therapy. Okay, terrific. And then just shifting gears briefly and sorry to do this, but just wondering about the commitments in narcolepsy Phase 3 and the second AXS-five Phase 3. Are you still anticipating that? Again, things seem to be changing daily based on the effects of COVID. I just want to know whether there's been any additional consideration with those 2 pivotal studies. Yes. We are moving forward as planned with our CNS pipeline. It is very robust. And with regards to trophilepsy, the plans have not changed at all with regards to launching our Phase 3 program and we're still on track to do that. So planning is still underway and everything is moving forward and is on track with regards to narcolepsy. Similarly, with AXS-five with our other planned Phase III trial, that is also moving forward. We gave guidance most recently that we expected that study to start in the 3rd quarter. And so we're moving forward. And with regards to COVID in general, we are in a very advantaged position that given that our efficacy trials which are needed for commercialization or which are needed to provide the first evidence of efficacy. For example, our advanced pivotal trial in all of them disease agitation, very advantage that all those studies have completed enrollment. And so we are in a good position. And the actual timing of the launch of additional trials, I think it does allow us certainly enough time to see how the impact of COVID hopefully wanes by the time that we plan to march those studies. Okay. Congratulations again on the data and thanks for the additional color. Thank you, Bert. Matt Kaplan with Ladenburg Thalmann. Your line is open. Hey guys, good morning and thanks for taking the question. Just wanted to dig in a little bit more to the differentiation of AXS-seven with respect, I guess given the momentum results where you clearly showed superiority, rizatriptan and now the INTERCEPT results. I guess maybe a question for Dave. Help us understand in terms of the reduction in the use of rescue meds and in terms of the durability of the pain freedom, how do you think this will play with payers and impact on, I guess, now momentum and intercept helping you to get on the different schedules with payers? Sure. Thanks, Matt. I think when we look at what payers are interested in, the type of data that we've generated, I think is really in line Look at what payers are dealing with kind of day in and day out, they're dealing with kind of a merry-go-round of triptans for many of these patients where they try 1, try another, try another and yet frustration with efficacy remains, disability remains, use of rescue medications remain. We have the ability to go in in a very unique position to say for many of those patients who've been on that merry-go-round of triptans, what's the next best use that you can look for an effective therapy that can change that future. And our superiority to rizatriptan really helps answer that question for many, many of those patients that are difficult to treat. So when you look at those data from MOMENTUM, you look at our ability not only to quickly deliver efficacy, but also then to sustain it, then of course that leads to the reduction in rescue medication. That has a great benefit to patients, but it also has a nice economic benefit too. So when you think of the overall cost of managing migraine, which has been estimated certainly in the neighborhood of $78,000,000,000 in direct and indirect costs in the U. S, then we think a big driver of that is the lack of efficacy. So we're in a very good position to come in, in a very differentiated stance in terms of our clinical data and then also have that available in a form that patients and clinicians prefer in an oral format and with a tolerability profile in these trials that have been very favorable. So I look forward to the discussions with payers. I look forward to delivering the type of clinical profile that we think they're interested in that delivers patient benefit, clinician benefit, but also clear economic benefit as well. Great. That's very helpful. Thanks for the color and congrats on the results guys. Thank you, Matt. There are no further questions at this time. I would now like to turn the call back over to Ariel for closing remarks. Thank you all again for joining us on the call today. We are very pleased with the additional data generated in the INTERCEPT trial for AXS-seven and these data confirm the superior and durable efficacy of AXS-seven and also it expands and enhances the differentiated profile of this product candidate in the acute treatment of migraine. We remain on track to file 2 NDAs by year end, one for AXS-seven in migraine and one for AXS-five in major depressive disorder. We look forward to reporting top line results for our pivotal ADVANCE trial in Alzheimer's disease agitation in early Q2. Thank you. This concludes today's Axsome Therapeutics conference call. We thank you for your participation. You may now disconnect.