Axsome Therapeutics, Inc. (AXSM) Earnings Call Transcript & Summary

Good morning, and welcome to the Axsome Therapeutics Conference Call. [Operator Instructions] As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Darren Opland, Director of Corporate Communications and Axsome Therapeutics. Please go ahead.

Thank you operator. Good morning, and thank you all for joining us on today's conference call to discuss the positive top line results from the SYMPHONY Phase III trial of AXS-12 in narcolepsy. This morning, we issued a press release announcing that AXS-12 achieved the primary endpoint in the trial. The release crossed the wire earlier and is available on our website at axsome.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 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, our commercial plans regarding Sunosi, Auvelity and our pipeline products, revenue projections 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 are Mark Jacobson, Chief Operating Officer; Dr. Herriot Tabuteau, Chief Executive Officer; and Dr. Michael Thorpy, Professor of Neurology at Albert Einstein College of Medicine. Mark will start by providing an overview of today's announcement before turning the call over to Herriot, who will review in greater detail the top line results of the SYMPHONY clinical trial. Following Herriot's update, Dr. Thorpy will offer a clinical perspective on narcolepsy and comment on the implications of the SYMPHONY study results. We will then open the line for questions about the SYMPHONY study data. Questions will be taken in the order they are received. And with that, I will turn the call over to Mark.

Thank you, Darren. Good morning, everyone, and thank you for joining Axsome Therapeutics SYMPHONY study top line results data call. We are very pleased to announce that AXS-12, Axsome's highly selective and potent norepinephrine reuptake inhibitor and cortical dopamine modulators achieved the primary endpoint in the SYMPHONY Phase III trial by demonstrating a substantial and statistically significant reduction in weekly cataplexy attacks compared to placebo. Additionally, AXS-12 achieved statistically significant remission of cataplexy. AXS-12 statistically significantly reduced excessive daytime sleepiness or EDS severity compared to placebo, assessed by the CGI-S. AXS-12 statistically significantly improved concentration in memory compared to placebo on the FOSQ-10. AXS-12 statistically significantly reduced overall severity of narcolepsy compared to placebo on the CGI-S for narcolepsy. AXS-12 statistically significantly improved overall function and quality of life compared to placebo on the FOSQ-10 total score. And AXS-12 was well tolerated in the trial. I would now like to turn the call over to Herriot, who will review the Symphony top line results in greater detail.

Well, thank you, Mark, and we are pleased to announce the top line results of the SYMPHONY Phase III trial of AXS-12 in the treatment of narcolepsy. Narcolepsy is a disabling disorder of sleep-wake control. Narcolepsy with cataplexy also called narcolepsy Type 1 is caused by a loss of orexin neurons which normally provide excitatory input to norepinephrine and dopamine neurons. Norepinephrine is important to the control of muscle tone during wakefulness in both norepinephrine and dopamine play an important role in sleep-wake regulation. The reduced norepinephrine activity resulted in loss of muscle tone or cataplexy and decreased norepinephrine dopamine activity results in reduced wakefulness and cognition. AXS-12, also known as Reboxetine is our selective norepinephrine reuptake inhibitor and cortical dopamine modulator. The resulting increase in norepinephrine signaling with AXS-12 may increase wakefulness as well as cognition and also specifically norepinephrine signaling we know improves muscle tone in many animal models. Now turning to the SYMPHONY study in more detail. The SYMPHONY study was a Phase III randomized, double-blind multicenter placebo-controlled trial in which 90 patients with narcolepsy type 1 were randomized to treatment with AXS-12 or placebo for 5 weeks. The primary endpoint was the change in the frequency of cataplexy attacks. Other measures of symptoms of narcolepsy were also assessed as well as safety and tolerability. Here is a look at the study population. The medium number of weekly cataplexy attacks was approximately 20 in both groups, indicative of a severely affected population. EFS scores at baseline were 17 to 18, corresponding to severe excessive daytime sleepiness. Patients have mean CGI-S score for both EDS as well as narcolepsy overall of approximately 5 at baseline. This corresponds to a markedly severe population. In addition, nearly 50% of patients endorsed symptoms of anxiety or depression. Turning now to efficacy results. AXS-12 met the primary endpoint by demonstrating a substantial and statistically significant reduction from baseline in weekly cataplexy attacks compared to placebo at week 5 with reductions of 83% in cataplexy attacks for AXS-12 and 66% for placebo with a p-value of 0.018. The improvement with AXS-12 was seen as early as week 1 with a reduction of 56% compared to a reduction of 31% for placebo with a p-value of 0.007. Now AXS-12 substantially induced remission of cataplexy defined as a 100% reduction from baseline. Remission was achieved at week 5 by 33% of the AXS-12 treated patients compared to 9.5% of placebo patients with a p-value of 0.008. Statistically significant achievement of remission was rapid, being experienced at week 2 by 24% of AXS-12 treated patients compared to 4.5% of placebo patients with a p-value of 0.008. Remarkably, the percentage of cataplexy free days a week 5 was 85% for AXS-12 versus 23% for placebo with a p-value of 0.014. Now turning to other symptoms of narcolepsy. AXS-12 significantly reduced excessive daytime sleepiness severity as assessed by the CGI-S scale for EDS compared to placebo at week 5 with a mean reduction of 1.8 points for AXS-12 compared to 0.9 points for placebo with a p-value of 0.027. Rapid improvement on the CGI-S or EDS was also seen as early as week 1 compared to placebo with a p-value of 0.006. AXS-12 concurrently improved excessive daytime sleepiness and cataplexy as compared to placebo. Concurrent EDS and cataplexy response was achieved at week 5 by 57% of patients treated with AXS-12 compared to 33% of placebo patients with a p-value of 0.029. Concurrent EDS or cataplexy response was defined by a 30% reduction in advertent naps and EDS response and a greater than 50% reduction in cataplexy attacks, the cataplexy response. A significant reduction in the number of inadvertent naps was experienced by 54% of patients treated with AXS-12 at week 5 compared to 28% of placebo patients as measured by the NSAQ. And a greater than or equal to 3-point improvement from baseline on the ESS was achieved by 60% of AXS-12 treated patients who had a cataplexy response. Turning now to cognition. AXS-12 significantly improved concentration in memory as measured by the cognitive function items of the functional outcome of Sleep Questionnaire or FOSQ-10 at week 5 with a p-value of 0.004. The AXS-12 concurrently improve cognition in cataplexy as compared to placebo, concurrent cognitive and cataplexy response was achieved at week 5 by 41% of patients treated with AXS-12 compared to 17% of placebo with a p-value of 0.016. AXS-12 improved narcolepsy overall disease conditions as well as patient function and quality of life. Clinicians reported a rapid and significant reduction in overall narcolepsy severity using the CGI-S for narcolepsy overall for patients with AXS-12 compared to placebo at week 5. This was statistically significant with a p-value of 0.007. AXS-12 also demonstrated significant improvement in overall patient function and quality of life as measured by the FOSQ-10 overall total score as compared to placebo at week 5 with a p-value of 0.005. Now both anxiety and depression are known narcolepsy co-morbidities, and they were reported by 45% of participants at baseline. AXS-12 treatment led to an improvement from baseline in the anxiety/depression domain of the EQ-5D-5L, which was achieved by 55% of patients treated with AXS-12 compared to 32% of placebo patients, which trended. Now let's take a look at the tolerability profile. AXS-12 was well tolerated in the trial, most commonly reported adverse events in the AXS-12 arm were dry mouth, nausea and constipation, which were all mild to moderate. The rates of discontinuation due to adverse events was low, just once -- with just 1 subject in each of the AXS-12 and placebo arms, and there were no serious adverse events in the trial. Now that we've run through the SYMPHONY top line results, I will now turn the call over to Dr. Michael Thorpy, who has joined us today to provide his expert perspective on the narcolepsy treatment landscape and his thoughts on the SYMPHONY study results. Dr. Thorpy, please take it away.

Good. Thank you. Good morning. Okay. I'm going to give you an overview of narcolepsy. Narcolepsy is a serious debilitating neurological disorder. It's a -- an often disorder is fairly rare, but it is still seen by up to 185,000 people in the United States who have this diagnosis. But it's believed that 50% of patients with narcolepsy are still undiagnosed. So the exact prevalence of narcolepsy is still not that clear. Now the majority of people with narcolepsy have the symptom of cataplexy, which is emotionally induced muscle weakness. And -- but the main symptoms of narcolepsy consist of excessive daytime sleepiness, abnormal REM sleep phenomena of which cataplexy is one of these features, but there's also sleep related hallucinations, including hypnagogic hallucinations and also sleep paralysis. As well as the abnormal REM sleep phenomenon, there is also disturbed nocturnal sleep. Now we divide Narcolepsy into 2 types, this type 1, which we're predominantly talking about today, which is patients who have narcolepsy with cataplexy. And then there's type 2, which are patients who have sleepiness, but no cataplexy. Now narcolepsy is a very burdensome disorder. It's associated with significant morbidity and mortality and health care utilization. So that patients with narcolepsy have more frequent hospital visits and control populations because treatment is primarily by medication, most of the patients with narcolepsy do take medication and take multiple medications. And so their medication use is greater than controlled people. Their health care costs consequently tend to be higher, twice as high as general populations. They also have the symptom of cataplexy, which is the emotionally induced muscle weakness that can cause them to have falls. And because of that and because of the sleepiness, they are more liable to injuries, particularly motor vehicle accident injuries, so 6x greater than the general population. And interestingly enough, the all-cause mortality has also increased in narcolepsy. Now there's a CRESCENDO study that was performed sponsored by Axsome, which looked at over 200 subjects who had narcolepsy type 1 and they looked at the patient burden, and they found that the narcolepsy was really affecting them on a day-to-day aspect so that the daily life was affected, 50% felt that it was a burden on their daily life. Cataplexy was also a significant factor for 60%. As I mentioned, because of the muscle weakness, they can fall down, which -- or get weakness in their legs that caused them to temporarily sort of a drop or lose muscle tone and this can happen in conversation with people. And so it's extremely embarrassing, 64% finding that an embarrassing symptom. And it also affects their professional career. So it can affect their education, it can affect their occupation. And this was mentioned by 65% of patients. And because cataplexy has many wide-ranging features to it, not only just weakness in the legs that can cause them to fall. But other more subtle symptoms, which are not that evident to an onlooker, but can be very distressing to the individual patient. And one of them is slurred speech so that they may get just slurred speech, and 68% found that to be a very embarrassing symptom. So the burden is very significant for narcolepsy. Now most patients with narcolepsy, as I mentioned, are on medications. The predominant medications being used out there are wake promoting medications such as modafinil, armodafinil and solriamfetol but also oxybate, which are one of the few medications that treat cataplexy and daytime sleepiness. And that's 47% of patients with NT1 tend to take oxybate. Stimulants, traditional stimulants amphetamines and methylphenidate are still quite widely used, although we generally regard them as a second or third line treatment for narcolepsy but 42% of patients are taking those and antidepressants are used by 38% of patients for their narcolepsy as well as their psychological problems. There are other medications that are used as well besides these in about 10% of patients. 37% of patients with NT1 do report being diagnosed with depression. And of those, 80% are on medications that are treating their depression. Now one of the reasons why we need new medications for the treatment of narcolepsy is that despite current treatments, there are still high rates of symptoms, and patients on current therapy for their narcolepsy indicate that they continue to have cataplectic episodes, 77%. They may not be as strong as they originally had a baseline and may not consist of falls, but they may have many of those symptoms that I just mentioned that can cause some huge embarrassment such as the slurring of speech or just transient weakness and 77% continue to have some cataplectic episode. 64% continue to have excessive daytime sleepiness, sleepiness is a very intransigent and narcolepsy, and it's a very difficult symptoms to treat and it's almost impossible to totally eliminate the excessive daytime sleepiness. There are 74% of patients continue to have concerns about cognitive impairment. Most patients with narcolepsy have cognitive impairment, and this is very resistant to medications at the present time. There's also disrupted nocturnal sleep, which does add to the patient burden in terms of their narcolepsy. So the implications of the SYMPHONY study are that AXS-12 was associated with a rapid and robust effect on cataplexy compared with placebo. And there was a major reduction in weekly cataplectic episodes and achievement of complete remission in 33% at 5 weeks of their cataplexy. So a major effect on cataplexy. AXS-12 also improved excessive daytime sleepiness, and this was supported by improvement inadvertent naps. So there's a reduction in inadvertent naps and there was a positive trend on the Epworth Sleepiness Scale. AXS-12 improved cognitive function is measured by the cognitive function items on the FOSQ-10 and this was also supported by improvement in the ability to concentrate. It -- AXS-12 significantly reduced the severity of narcolepsy overall, overall symptoms as measured by the clinical global impression scale of severity and significantly improved quality of life and function as measured by the FOSQ-10. As mentioned earlier, depression and anxiety are known co-morbidities of narcolepsy and the mechanisms of action of AXS-12 obviously have specific relevance to those particular conditions. And AXS-12 also showed a very favorable safety and tolerability profile. So based on these results, AXS-12 would represent an important new treatment option for physicians and for patients in their fight against narcolepsy. Thank you. I think we're now opening it up for questions and answers.

[Operator Instructions] The first question today is from the line of Leonid Timashev with RBC Capital Markets.

Congrats on the data. I guess can you maybe talk a little bit more about the ESS sleepiness endpoint. I guess, how important is the sleepiness benefit both from the perspective of physician who's prescribing it, but also from a commercial standpoint? And to what extent is the results on the CGI sleepiness scale important and indicative of the overall trend for sleepiness?

Sure. Thank you for the question. I think this is a clinical question. So Dr. Thorpy, do you have any thoughts there?

Yes. Well, sleepiness, obviously is a major symptom of narcolepsy, and it's a very important one. And I think that the data that we're seeing with the AXS-12 shows that it is effective at improving that endpoint, the secondary endpoint of excessive daytime sleepiness. So that -- the amount of change that we're seeing and the reduction in the inadvertent naps is extremely important. And the fact that this medication has such a robust effect on cataplexy shows that it's a primary potential treatment for patients who have type 1 narcolepsy who have both the cataplexy and sleepiness. So we're seeing that improvement in the excessive daytime sleepiness. So I don't have the data available at the moment on terms of the actual change in Epworth Sleepiness Scale, but on the other measures that you mentioned. We are seeing significant improvement in daytime sleepiness, although this was not the primary endpoint of the study.

The next question is from the line of Ram Selvaraju with H.C. Wainwright.

I wanted to ask about the potential competitive advantage provided by the impact that you see with this drug on concentrations and cognitions, and the extent to which this might be a therapeutic benefit that is not offered by other drugs currently available for the treatment of narcolepsy?

Good. Thank you for asking that question actually because this is an area that is of particular interest to me. One of the features of narcolepsy, as mentioned, is there's impairment in terms of cognitive function. And all -- virtually all patients mentioned this, but we have not specifically addressed this with medications in the past. And the medications have been focused on the cataplexy and the excessive daytime sleepiness. So I think this is a very important finding in this study that there is improvement in this cognitive function of these patients and concentration. So I think this is a very important factor in management of patients with narcolepsy. And certainly, patients that maybe are on other medications that are doing well in terms of their cataplexy in the excessive daytime sleepiness. We do find that these patients, as shown in the CRESCENDO study that they still have complaints with regards to their cognitive function and concentration. And so any additional improvement that we can gain in those symptoms, I think, is extremely important in narcoleptic patients. So as I say, I'm delighted you asked that because it is an area that has not been addressed in the past, and this study does look at that specifically and does show significant improvements, which I think is very important for these patients.

The next question is from the line of Marc Goodman with Leerink Partners.

This is Basma on for Marc. Could you please remind us what we know so far about the long-term side effect profile of AXS-12 based on the published data? Should we expect the AEs like sexual dysfunction and others similar to the AEs known with the SNRI class? Or were there any differentiation that you would like to highlight for us?

Sure. So I'll take that question. So in terms of the side effect profile, we were very pleased with the side effect profile, very well tolerated. There was no signal in our study for sexual dysfunction. We also have an open label CT extension trial with AXS-12, the vast majority of patients from this study have rolled over into that trial. Patients are being treated long term for an additional 6 months. And thus far, tolerability profile has been maintained. So it's great to have to generate our own data, and we will continue to generate additional safety data.

The next question is from the line of Joon Lee with Truist Securities.

Congrats on the data. Where do you see AXS-12 being slotted in the narcolepsy treatment paradigm? And do you think the profile you reported today justifies being used ahead of generic SSRIs without much pushback from the peers?

From point of view of the role of reboxetine in treatment of narcolepsy, I think it's going to vary from patient to patient because these patients have a different constellation of symptoms. There are some patients that are extremely incapacitated by their cataplexy and the robust effect of AXS-12 shows that it will be very important for those patients and may be used as a first-line treatment and those that have severe and capacitating cataplexy. The fact that there is some additional improvement in daytime sleepiness is an added benefit to this. And so as a sole agent, it could be used as a first-line drug for many of these patients with type 1 narcolepsy. But also, I think that -- as mentioned, many patients are on a variety of different medications and has shown some of them are the wake-promoting agents, some of them are really oxybates. And they continue to have some symptoms. And so I very much see this medication being used as a second-line treatment as well, an add-on treatment. So those patients that may be treated with the only FDA-approved drugs at the present time for the treatment of cataplexy which are oxybates and pitolisant, this could well be an add-on medication to those treatments to bring about further improvement. Plus the effect on cognition, and I go back to that because we were -- I was talking about that earlier, that I think the cognition effect is very important and has not been addressed by the studies previously. And this beneficial effect -- and the fact that it is an antidepressant when these patients have such high co-morbidities of mental disorders, including anxiety and depression is, again, another important factor. As we've shown in the data about 38% or so of patients with narcolepsy are currently on antidepressants, not only for narcolepsy, but also for their mental disorder. And so having a medication has been shown to be effective for narcolepsy that also has some beneficial effect, although the study wasn't powered, obviously, to show significant improvements in anxiety and depression, the fact that it is an antidepressant and has shown some benefit in those domains means that it's going to be extremely helpful for many patients with narcolepsy. As compared with other medications, as you mentioned, there are many other serotonin reuptake inhibitors, norepinephrine reuptake inhibitor out there, but none of them are FDA approved for narcolepsy. And so if this drug gets to be FDA approved, then obviously, it would have an advantage of those other drugs, which have never been really studied properly. There are no good studies on any of the antidepressants other than with this drug in the past in narcolepsy. So this is the only data that we really have showing the efficacy of this type of medication in the treatment of narcolepsy. So as for the cost factor, I really am not in a position to answer that. I mean I'm not sure how our insurance companies will handle it. But I think that the fact that this has shown a benefit in both cataplexy and sleepiness and in the cognitive domain makes a big advantage over any unproven antidepressant medication that might be out there.

Our next question is from the line of Jason Gerberry with Bank of America.

Firstly, just on the primary endpoint, the size of the placebo-adjusted delta was, I guess, smaller than some of the FDA-approved narcolepsy medications. So just wondering if you have any hypotheses around sort of what drove that high placebo response? Or was it just bad luck in terms of seeing such a high placebo response on the cataplexy reduction. And if the view is ultimately that the totality of data is really important. If you can just remind us what are the key secondary endpoints in this trial that could be candidates for label inclusion?

Thanks for the question. So if you -- with regards to the placebo response, as you know, that does vary by studies. And one of the things that drive the placebo response is expectation bias. So we did have a positive Phase II trial with AXS-12. So that could have driven the high placebo response. But I think the strength of the data is that even with such a high placebo response, that it separated very nicely. An 83% reduction in cataplexy attacks is almost total elimination of the cataplexy attacks with AXS-12. So very, very strong results. The -- what we -- we did go through a lot of the endpoints, which were included. This is a small study and because this is an orphan condition. So you would not expect it to be powered for any of the other endpoints. But as you can tell, we did look at endpoints related to excessive daytime sleepiness, cognition was really important for us based on the mechanism of actions, we looked at that. And with regards to what would be included in a label, that's always a negotiation with the FDA, the indication which we are studying the drug for, for the initial indication is cataplexy.

The next question comes from the line of Joseph Thome with TD Cowen.

Congrats on the data. Maybe just in terms of the regulatory submission here, can you comment on the expected timing of the completion of the open-label extension safety database? Obviously, you did have the prior breakthrough therapy designation. Is it your expectation that this would be the final Phase III efficacy study that will be needed for a submission. And maybe if you can give us an idea when that application could be submitted?

So this is the final Phase III trial, which we will need to submit the NDA and we currently are conducting an open-label safety extension trial, as you mentioned. The way to think about that is that the patients who just completed this study have rolled into the open-label safety extension trial, and they'll be treated for 6 months. So that's going to be the gating factor. We'll be ready, of course, to submit the NDA, and we would expect being able to submit it approximately within 6 months of completion of the open-label safety inspection trial.

Our next question is from the line of David Amsellem with Piper Sandler.

So can you talk about competitive positioning versus pitolisant or WAKIX given that, that product is approved in cataplexy? And maybe just talk through your overall impression of the anti-cataplectic effect of reboxetine relative to the body of data for pitolisant?

Sure. So I'll let -- maybe Dr. Thorpy comment on the extent of the cataplexy effect and how we've used that clinically. And then with regards to the competitive question, the way that we look at it is this is a market which is highly underserved. And the results of the CRESCENDO survey show the vast majority of patients still continue to experience symptoms. And so we're happy to provide another treatment option, and we were happy to also generate data on these various domains, which are important for patients. Dr. Thorpy?

Yes. So pitolisant is a medication for those of you that are not familiar with FDA approved for treatment of both excessive daytime sleepiness and cataplexy in narcolepsy and it is a daytime medication. The effect in terms of cataplexy with AXS-12 is very strong. I mean, 33% had a 100% remission in terms of their cataplectic episodes at 5 weeks. So that's a large number with complete remission because, as mentioned earlier in my presentation that a significant number of patients continue to usually have symptoms of cataplexy. So we're seeing a large effect. I think pitolisant is being used. It's largely being used as an add-on medication to other medications, although it can be used as a first-line treatment for type 1 narcolepsy patients, but very often is used to [ set on ] to, say, oxybate, for example, which is the major benefit in terms of the symptoms of narcolepsy and then pitolisant adds to that effect. I think that in general, the effect on cataplexy is good with pitolisant, although I think -- and I don't have the comparative data here and there, of course, there are no comparative studies with pitolisant and AXS-12. But I would think that the effect of AXS-12 based on the results that we've seen is very strong in comparison with pitolisant. So I would see both of these medications being used not only as first-line drugs, but also as add-on drugs, and I see reboxetine having that additional benefit on the cognitive function that we've talked about in addition to its effect on cataplexy. So I think in comparison with other anti-cataplectic agents out there, I think we're seeing a very robust effect with AXS-12.

Our next question is from the line of Charles Duncan with Cantor Fitzgerald.

Congrats on these results. I had a question for Dr. Thorpy and that is related to the patient population that was enrolled in this study, do you think that it is representative of the broader population. And really, what I'm wondering is the sample size sufficient to compel you to prescribe. What do you think about the response rate versus remission? What is the more, I guess, compelling results? And then just one clarification for management. That is relative to the use of other drugs, was there a wash out? And did you allow for a change in background medications during the study?

Okay. So as mentioned, yes, there was a washout of anti-cataplectic episodes in the study and the patients were allowed to continue with their wake-promoting medications modafinil, armodafinil, so that may have had some effect on the assessment in terms of excessive daytime sleepiness because those medications are used for that. But despite that, we did see a beneficial effect on excessive daytime sleepiness despite them being on that. As for the numbers, yes, the numbers are relatively small or 46 patients being on active medication. These patients, let me just emphasize, they are all type 1 narcolepsy patients, many other studies that are done in narcolepsy have been combined NT1 and NT2 patients, but this is all type 1 patients. And the -- it's a parallel design study. So there were nearly 100 patients on with NT1, which is a large number of patients considering this is a relatively rare orphan disease. So I think the effects that we're seeing in terms of the effects on cataplexy are relatable to a larger population if we were to do it. I think that the effect size that we're seeing here is very good. I mean, a reduction from nearly 20 cataplectic episodes a week to down below 5 episodes a week and 33% with total remission. I think at 5 weeks, I think that's a very robust effect in terms of cataplexy. There was -- I'm not sure that I've answered all of your questions. So is there another point -- another part of your question that I didn't answer?

No, I think you got it. And then just clarification, did you allow for a change in background meds over the course of the study area?

I'm going to pass it back to Herriot to answer actually what happened with regards to treatment throughout the study.

No. We did not. As is normal during these types of clinical trials, you want to make sure that patients are stable, as stable as possible on the meds that they are on and that they remain on those meds to avoid confounding of the study results.

The next question is from the line of Joel Beatty with Baird.

Congrats on the data. The question is for AXS-12, you anticipated that this drug will stay as a treatment for certain patients with narcolepsy or could it follow the lead of Sunosi in which an initial indication related to narcolepsy paved the way for multiple other indications?

We just got the data. And the reason why I say that is one of the nice things about conducting clinical trials is you can mine the data to look for potential effects and use that information to inform thinking about other potential indications. So we just got the data. We're very pleased with the results. Right now, our focus is to make sure that the clinical benefit that we've seen in the study for narcolepsy patients actually gets out there into the hands of clinicians and patients. So that's going to be our focus, and we want to make sure that we execute on that.

The next question is from the line of Graig Suvannavejh with Mizuho Securities.

Congrats on the data. My question is just could you just remind us of the company's thinking on the positioning of AXS-12 for narcolepsy vis-a-vis Sunosi narcolepsy? And what are you currently thinking about in terms of the commercial strategy and how you'll position to?

Thanks for the question. We're -- so with both Sunosi as well as AXS-12, we now have 2 products with demonstrated efficacy in narcolepsy. So we're very much committed to the space. The -- both products have their strengths. As a reminder, Sunosi is approved to treat excessive daytime sleepiness in patients with narcolepsy. It is not approved for cataplexy and AXS-12, the primary indication would be treatment of cataplexy. So the products are definitely complementary and also it's complementary from a sales force focus perspective, from a commercial perspective and from a company-focused perspective on neuroscience and sleep disorders.

Thank you. We have time for one additional question. And that question will be coming from the line of David Hoang with Citigroup.

So I just wanted to ask about the type 2 narcolepsy population. Is there any, I guess, read through to that population from these data today? And then to what extent has there been off-label prescribing in the narcolepsy population?

Yes, let me answer that. The type 2 narcolepsy population, as mentioned before, patients that don't have cataplexy. Type 2 patients do have abnormal REM sleep phenomena of which cataplexy is just 1 manifestation, the most severe manifestations. So they do have abnormal REM sleep behaviors such as sleep-related hallucinations, sleep paralysis, very vivid frequent dreams that might very distressing REM sleep phenomenon. And I think the robust effect that we're seeing with the AXS-12 in terms of cataplexy relates to the fact that it is affecting REM mechanisms because cataplexy is a REM mechanism. And so it's going to have a beneficial effect on those other symptoms. So there is the potential that this drug could be very effective also in patients with type 2 narcolepsy and particularly those that have a combination of those abnormal REM phenomena plus the daytime sleepiness. And also patients with Type 2 do have the other co-morbidities, so we've talked about in terms of impaired cognition and memory and also having the psychiatric co-morbidities of anxiety and depression and -- which there is evidence for a trend towards improvement there, although it wasn't powered for that purposes. So I think this medication will be -- although if it's approved for cataplexy in narcolepsy, it has the potential for being used off label for the treatment of patients with NT2 narcolepsy who also have abnormal REM sleep phenomenon in those psychiatric co-morbidities and cognitive impairment. So I think the potential is there, and I would hope that Axsome maybe in the future, could or would look at that population as well, the NT2 population because I personally think that there is a potential for benefit in that group.

Thank you. At this time, I will turn the call back over to Axsome's CEO for any concluding remarks.

Well, thank you, Dr. Thorpy for your time today. I want to thank the rest of the audience for joining us on today's update, on the SYMPHONY Phase III clinical study. We are pleased to report positive top line results today with a strong set of data that confirm the promise and potential of AXS-12 for the treatment of narcolepsy. We look forward to completing the ongoing open-label safety extension trial of AXS-12 as we work to bring this treatment to the individuals with narcolepsy, and we look forward to sharing further results from the SYMPHONY study at upcoming scientific and medical conferences. I hope you all have a great rest of your day.

This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation.