Axsome Therapeutics Inc (AXSM) 2020 Q3 法說會逐字稿

Thank you, operator. Good morning, and thank you all for joining us on today's conference call. Our earnings press release providing a corporate update and details of the company's financial results for the third quarter of 2020 crossed the wire a short time ago 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; 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 made only as of today's date, and the company disclaims any obligation to update such statements.

Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Lori Englebert, Senior Vice President, Commercial and Business Development; and Dr. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs. Herriot will first provide an overview of the company and then review recent development and upcoming milestones. Following Herriot, Lori will comment on our commercialization approach, and then Nick will review our financial results. We will then open the line for questions.

I shall now turn over the call to Herriot.

Thank you, Mark. Good morning, everyone, and thank you all for joining Axsome Therapeutics Third Quarter 2020 Financial Results and Business Update Conference Call. Over the past several months, we continued to advance our AXS-05 and AXS-07 product candidates towards NDA submissions in major depressive disorder and migraine, and we intensified our commercial launch readiness activities. Committed capital from our recently announced term loan facility, combined with cash on hand, approached $400 million, strengthening our balance sheet through these anticipated commercial launches.

In the quarter, we also advanced the rest of our late-stage pipeline, including 2 positive FDA Breakthrough Therapy designation meetings for AXS-05 in Alzheimer's disease agitation and AXS-12 in narcolepsy. And we scheduled an FDA meeting for AXS-14, our product candidate, for the treatment of fibromyalgia. Our intellectual property portfolio continues to grow with recently issued and allowed patents for AXS-05 in depression now extending to 2040.

We anticipate an active next few months as we complete our NDA submissions for AXS-05 and AXS-07, release top line efficacy data from open-label trials with these product candidates, initiate Phase III trials for AXS-05 and AXS-12 in Alzheimer's disease agitation and narcolepsy, and meet with the FDA on AXS-14 for fibromyalgia.

I will provide a brief pipeline update before handing it over to Lori, who will discuss our commercialization strategy for AXS-05 in depression. Then Nick will discuss our financial results.

Starting with AXS-05, our novel oral NMDA receptor antagonist. Pre-submission activities for the NDA for AXS-05 for the treatment of MDD are nearing completion. We expect to submit the NDA in January instead of by year-end, reflecting a COVID-19-related logistical delay from one vendor. We have completed a Phase III open-label long-term COMET safety trial of AXS-05 in depression. The 3 Phase II open-label efficacy sub-studies of the COMET trial have also been completed, and we are on track to report top line results from these efficacy studies by year-end.

Our placebo-controlled MERIT trial in TRD, or treatment-resistant depression, is on track to report results in the first half of next year.

Moving on to our program in Alzheimer's disease agitation with AXS-05, which received FDA Breakthrough Therapy designation in June. Results of the subsequent breakthrough therapy meeting for this indication confirmed the pivotal status of our positive completed ADVANCE-1 trial. Consequently, only one additional Phase III trial is needed to support the filing of an NDA for AXS-05 in this indication, and we remain on track to initiate that study before year-end.

Switching now to our migraine program with AXS-07. The major NDA-related items are on track for completion by year-end. We now plan to submit the NDA in the first quarter of 2021 versus previous guidance of the fourth quarter of 2020 in order to allow for inclusion of supplemental manufacturing information. We believe that this approach will enhance the robustness of our submission.

We have completed the MOVEMENT Phase III open-label long-term safety trial of AXS-07 in migraine. We now expect to announce efficacy results from this trial in the fourth quarter of 2020.

Moving next to our narcolepsy program with AXS-12, which received FDA Breakthrough Therapy designation in August. We recently announced the expedited development status and plan for AXS-12 following a breakthrough therapy meeting. One Phase III efficacy trial, which, along with the previously completed Phase II CONCERT trial, will be used to support the filing of an NDA for approval of AXS-12 for the treatment of cataplexy in narcolepsy. We remain on track to initiate this Phase III trial in the first quarter of 2021.

Ahead of the potential launches of AXS-05 and AXS-07 starting next year, our commercial readiness activities have been accelerating. These activities include the build-out of our proprietary Digital-Centric Commercialization, or DCC, platform. Our partnership with Veeva Systems announced yesterday will provide digital technology that will be incorporated into the DCC platform. We are excited both by the clinical profile of our product candidates and our planned commercialization approach.

I will now turn it over to Lori, who will provide some observations as it relates to the growing need in depression and some insights into our planned commercialization approach.

Thank you, Herriot, and good morning, everyone. We are excited to talk to you this morning for the first time about our commercialization plans. As you may have noticed, yesterday, we announced a partnership with Veeva to help build our proprietary Digital-Centric Commercialization platform. I will speak more about why we believe this commercialization approach makes sense for us later. But first, I'd like to remind everyone why we believe AXS-05 has the potential to have such a significant impact on the MDD market.

We are increasingly excited about the opportunity to meaningfully change the way physicians view what's achievable with the pharmacological treatment of depression and to have a lasting impact on patients.

It should come as no surprise that the pandemic is having a profound effect on people. One of the most striking effects is the sharp rise in depression. Results of an epidemiological study recently published in JAMA, demonstrated that the number of U.S. adults with depression symptoms has increased 300% versus prior to the pandemic. This increase is even more notable given the prevalence of depression was already high pre-pandemic. The increase is heavily skewed towards individuals who are already in the moderate to severe depression category.

On top of the sharp increase in prevalence, the MDD market still has extremely high unmet needs. Through primary market research with physicians and patients, 4 areas continually identified as high unmet need are, one, physicians want new, different, patient-friendly approaches to treatment. While there are many approved agents, all current oral antidepressants work primarily through the monoaminergic system. Two, physicians and patients want faster onset of action. Most commonly used therapies today take 6 to 8 weeks to reach therapeutic effect. Three, physicians want better opportunities for remission. We know through published research that only about 1/4 of patients on a standard antidepressant achieve remission more than a 10- to 14-week time frame. And four, patients and physicians want to stop trading off efficacy for safety and tolerability.

Current standard antidepressants typically are associated with weight gain, increased sexual dysfunction and cognitive impairment. If successfully developed, AXS-05 has the potential to address these unmet needs and bring meaningful advancements to physicians and patients for the treatment of MDD. Since the approval of tricyclic antidepressants in 1959, there have been no new oral mechanism of action for MDD. As an NMDA receptor antagonist, AXS-05, if approved, will be the first new oral mechanism of action for the treatment of MDD in over 60 years.

In clinical trials to date, treatment with AXS-05 has been associated with rapid release of depression symptoms, including achievement of remission as compared to both placebo and active comparators. Importantly, benefit was seen in both patient and physician-reported outcomes. AXS-05 was well tolerated and was not associated with weight gain, increased social dysfunction or cognitive impairment in our trials.

As I mentioned earlier, yesterday, we announced a partnership with Veeva to help build our proprietary, Digital-Centric Commercialization, or DCC, platform. The Axsome DCC platform incorporates specialized digital tools, proprietary data and analytics, integrated systems and an intelligent operating model. The goal of using evolving technology and digital execution is to optimize physician and patient engagement and thereby increase the effectiveness and efficiency of our promotional efforts as compared to traditional approaches.

Using a Digital-Centric Commercialization approach will, one, allow us to make extensive use of remote detailing, have real-time data fed to seamlessly integrated platforms that use sophisticated technology to allow our reps to make informed dynamic decisions; and two, allow us to leverage the evolving digital ways in which patients and clinicians access information.

The decision to take this Digital-Centric Commercialization approach was data-driven. On this slide, we highlight some key HCP trends that give us confidence we are taking the right approach. One, remote detailing, which was about 10% pre-COVID, has increased significantly and is leveling out around 50% of all engagements. Two, psychiatrists, our primary physician target for AXS-05, have been the heaviest adopters of remote detailing. As of the end of September, 63% of all visits to psychiatrist offices were remote. And three, remote detailing appears to result in significantly longer engagements with physicians, with a remote detail averaging around 25 minutes versus less than 5 minutes for traditional in-office call. This is an indicator that physicians are becoming more comfortable with the approach and that remote calls can be highly effective.

Key trends for consumers are very clearly trending towards digital. As shown on the chart on this slide, time spent with digital media has been rapidly increasing in the U.S. in recent years, surpassing traditional media for the first time in 2018. And within just 2 years, digital media time is already 25% higher than traditional media. This is a trend that we expect to continue to grow.

We believe that the macro trends around the current mental health crisis, virtual detailing adoption by physicians and the increased reliance on digital by consumers are unlikely to change after the pandemic.

Given what we know about the marketplace, HCP and consumer trends, combined with the potential for AXS-05, our initial launch engagement strategy will include an extensive use of remote detailing, augmented by conventional detailing as needed and primarily focused on psychiatrists and mental health-focused PCPs. We believe that this approach will not only increase quality and effectiveness but also significantly reduce the cost per physician interaction, providing greater flexibility in rep number and reach.

For patients, we intend to focus our engagement on using a digital omnichannel approach. We are very excited about our first launch and believe our Digital-Centric Commercialization, or DCC, platform approach is not only scalable but also relevant for all follow-on launches. This approach should provide HCPs and patients meaningful engagements that are optimized and differentiated. I look forward to sharing with you more about our plans in the future.

I would like to now turn over the call to Nick, who will provide a financial update.

Thank you, Lori, and good morning, everyone. Today, I will discuss our third quarter 2020 results and provide some financial guidance. We ended the third quarter with approximately $202 million in cash compared to roughly $191 million at the end of the second quarter, a net increase of approximately $11 million due to the net proceeds from our new term loan facility with Hercules Capital.

R&D expenses were $14.8 million for the quarter ended September 30, 2020, versus $15.8 million for the comparable period in 2019. The decrease of $1 million was driven by the completion of the majority of our clinical trials, which were ongoing in the comparable prior period.

G&A expenses were $6.3 million for the quarter ended September 30, 2020, and $3.1 million for the comparable period in 2019. The change was primarily due to an increase in noncash-related stock compensation expense, along with the continued build-out of the commercial function.

In the quarter, we secured a $225 million term loan facility with Hercules Capital. This committed nondilutive capital further strengthens the company's balance sheet and gives us additional financial flexibility through the anticipated potential commercial launches starting next year.

We believe our current cash position of over $200 million, along with the committed capital from our $225 million term loan facility, is sufficient to fund our anticipated operations based on our current operating plan into at least 2024.

That concludes our third quarter 2020 financial review. I will now turn the call back to Mark to lead the Q&A discussion.

Thank you, Nick. Operator, may we please have our first question?

(Operator Instructions) We have our first question from Charles Duncan with Cantor Fitzgerald.

Congrats on a good quarter of progress. Looking forward to more in the near term. Have a couple of questions for you. I'll try to be brief. The first is relative to the long-term safety studies for both 05 and 07 COMET and MOVEMENT. I'm wondering if you can provide some color on the completion rates or persistence because it seems to me that -- I know those are safety studies, but in both cases, patients staying on drug is going to say something about the perception of efficacy or lack of tolerability issues in -- for the patient over time. So wondering if you can give us some color on that. And then I have a follow-up.

Good morning, Charles. Thank you for the question. That is certainly something that we've looked at. As a reminder, both of these studies dosed patients over a 1-year period. So that's a long time. And then one of the things that you have to do when you run studies like that is you've got to make some baseline assumptions as to what the rates would be of discontinuations. And what we can tell you is that we've been pleased with the persistence rates and that the rates of discontinuation throughout the study have been lower than what we expected. We do intend to announce results of these studies or of the sub-studies, in the case of COMET, by year-end. And at that point, we'll have more information for you.

Okay. That's helpful. So you feel like patients are remaining on the study, perhaps even greater amount than you had anticipated?

So we'll have greater details for you when we report out the results of the study. But certainly, in terms of the assumptions that we made for what you would expect to be the drop-off rate over a 1-year period, we were pleased that it was longer -- I'm sorry, it was -- we were pleased that what we actually observed was lower than what we had projected.

Okay. That's helpful. And then I wanted to move on to AXS-05 in Alzheimer's agitation. I listened to Cedric's presentation yesterday at CTAD, and I noted that you plan to start another -- well, a Phase III, the only one needed to move forward in -- by the end of the year. And so when you look at that presentation at CTAD, it seemed like the responder rate was notable. And so I'm wondering if you can provide any color on what you thought the key takeaway was with AXS-05 in Cedric's presentation yesterday at CTAD?

Sure. So we were excited to present the results of the ADVANCE trial at a scientific forum. So we presented it before, but certainly, CTAD is one of the premier forums for Alzheimer's disease-related illnesses. And the key takeaways are -- this is a rare finding, having efficacy in this patient population in this indication. So we were very pleased with the results of the ADVANCE-1 in trial. And not only was there a very significant reduction in symptoms, but the reduction was clinically meaningful.

One of the takeaways when you look at the data, we thought, was the fact that the average reduction from baseline symptoms is about 50%. So very strong set of results. And of course, not only do you want to control symptoms, but you want to make sure that the safety profile is there and that the drug is well tolerated, especially in this vulnerable population. And so we're pleased with that outcome, too. And I'll let Cedric maybe make some comments, if he has any, with regards to the reaction from the forum and thereafter after our presentation from the scientific community.

Yes. Hi, Charles. Thanks, Herriot. And the main takeaway from the CTAD was there was a great level of interest. At one point, the attendees numbered close to 600. So that was really great. We were encouraged by that. And then as Herriot said, the translation of the improvement in symptoms on the primary outcome measures, the CMAI into clinically meaningful response rates. And I think the fact that there is no drug approved for AD agitation had a lot of people excited with the data.

And then of course, from a safety perspective, not associated with sedation or cognitive impairment, so important to this patient population, high rates of completion in the study and low rates of fall similar to placebo, which was also good. So I think taken in totality, people are looking forward to the next trial and the continued development for -- with AXS-05 in this indication.

Yes. In that presentation, you mentioned that the trial was being designed. I imagine you're probably pretty far down the process of doing that. Can you provide some color on what that next Phase III looks like in terms of size or timing and endpoints?

So Charles, we're very close to providing all that information because as we mentioned in our prepared remarks, we are on track to launch that confirmatory Phase III trial this year. What we have disclosed, of course, are general parameters around the design, which will be a randomized withdrawal design. And so we like that design feature. This will be placebo-controlled. And that relates to your size question. Since this will be a 2-arm trial, we would expect it to be smaller than the last study just by the fact that it's 2 arms versus 3 arms. But we'll provide you additional details soon as we get ready to start the study by year-end.

We have a question from Marc Goodman with SVB Leerink.

Yes. So Herriot, can you just give us a little more color on 2 issues? One, you mentioned that 05 has been delayed into January because of one vendor. How much are we on top of that situation such that you're very confident that it's only going to be delayed into January? Or is this one of those things where it's a little open-ended?

And then the second issue was the -- for 07, you talked about the NDA in the first quarter, including extra manufacturing information. Can you give us kind of the same sense of confidence that -- as my first question, with respect to what's going on here? Maybe you can give us a little more color on how much we're on top of it and it's definitely going to be not any more delayed than that.

So thanks, Marc, for those questions. With regards to AXS-05, it is one vendor. And the logistical issue is very straightforward. Because of COVID-related backup, they are not able to deliver a report to us until the very end of December. So that's later than we had expected. So we're on top of it, and we'll definitely get that by the end of December, but we wanted to make sure that we let you know that it could slip into January. So we're pretty confident that we'll be able to file it in January. So it is one isolated vendor, and it is only a report.

So with regards to AXS-07, this is a little bit of a different situation here. This is a situation whereby, by the end of the year, we will have completed all the major activities which are needed to file our NDA, and we're on track to do that. And because of the unique manufacturing behind the MoSEIC technology, we want to make sure that we have as robust as possible of a submission package. So we continue to generate data. And the question is how much do you include. And since we will be having some data in the early part of the year, we'd love to be able to include that in the package. But to provide some additional color on that, I'm going to turn it over to Mark Jacobson.

Good morning, Marc. So just want to be clear, this is not the result of a manufacturing or stability issue or anything like that. It’s exactly as Herriot said that we will have data available that, we think, would add to the submission, given it's a novel delivery technology. And so that will just allow us to make the package as robust as possible.

(Operator Instructions) We have a question from Yatin Suneja with Guggenheim Partners.

I have 2 questions. First, with regard to the MERIT study, can you maybe -- I think you did make some comment, but I missed it, but can you maybe just talk about what characteristics of the drug you need to further elucidate before you start a Phase III in TRD? And then do you actually need a Phase III or maybe this one could be sufficient? So that's one piece.

And then with regard to the COMET disclosure that we're going to have, again, this is going to be nonplacebo-controlled. So just trying to get a sense of what level of disclosure you will make and how should we interpret those data given lack of placebo arm in the study.

Thank you, Yatin. So with regards to the MERIT trial, the -- this is a study in TRD. It is a randomized withdrawal study. And so that will give us some new information with regards to 05 in that study design because all of our prior studies have been parallel group studies. This -- these data will supplement the data that we will be releasing by year-end from our COMET TRD trial, which is open-label, as you mentioned.

But with regards to TRD, remember that the label that we'll be filing for is MDD, which is the broadest indication. And that includes all subsets of major depressive disorder, which includes patients who failed one antidepressant or patients who failed 2 or more antidepressants who would -- who may be classified as treatment resistant as well as in patients who have suicidal ideation, et cetera.

So we have a broad label which captures the entire spectrum of MDD patients. And the point of the MERIT trial as well as the COMET sub-studies is to provide data to clinicians in terms of how the product performs in these various populations. So by the time that we launch the trial, we hope to have -- we will have -- we hope to have these data -- some of these data published and, certainly, we'll be sharing them with you before year-end.

Now for the COMET sub-studies, as you mentioned, so these are open-label trials, but we do measure efficacy, and we do expect to get meaningful data from those studies. And the reason for that is they reflect real-world use. This is how patients are treated by clinicians. And every day, when patients are treated by clinicians for their depression, the clinicians have to assess whether or not the patients are responding and how well they are doing. And typically, what clinicians do is they look at improvement in symptoms.

There are some objective measures, too, which really do not depend on a comparator group, such as remission rates, rates of clinical response and clinical response defined as at least a 50% reduction in symptoms, onset of actions, do patients get better faster. So all those things are assessable by clinicians, and those are the types of measures which we'll be looking at and which we'll be providing data on when we report out these results by year-end.

Got it. And just one quick question on the P&L. I mean I see the R&D line ticked up a little bit, but G&A still remains pretty reasonably low. When -- at what point should we see an inflection on G&A, given that you would have to build infrastructure around the 2 launches? How should we model that? And then just if you can comment on the R&D. Is it going to trend up given that there are more studies, but there are some finishing also? Just if you can help us with the modeling a little bit, it will be great.

Thanks for the question. This is Nick Pizzie. So related to your first question, when can we see a pickup in G&A costs? Obviously, there's a lot of work that's going on right now from the commercial function. And we do expect to see probably a bump in the SG&A costs starting in Q1 as we prepare for launch readiness.

Our next question comes from Joseph Thome of Cowen & Company.

The first one on Alzheimer's agitation. If you could just give us -- I know there are others that are looking at more episodic treatment for acute agitation associated with Alzheimer's. Could you just give us -- based on your research, could an episodic product and a chronic treatment be used in combination? Or would these be sort of 2 separate subsets of patients? And then second, on AXS-07, looking ahead to that launch, we touched on AXS-05, would this remote and virtual launch plan be amenable to AXS-07 in migraine and with neurologists? Or would you have to kind of tailor the approach when it comes time?

Hi, Joseph. Thank you for the question. So what's -- I think an important characteristic to remember about AXS-05 in AD agitation is this is a -- this is a treatment which would be chronic, and the goal of that treatment would be to prevent patients from actually ending up in an institution, whether that be a nursing home or a hospital ER because their symptoms are uncontrolled. So from that perspective, I guess there is no reason, a priori, that various treatments, let's say, treatments for very acute disease, which results in patients needing additional care, there's no reason to think that our product would not be used with other treatments. That's normal.

And then with regards to your question around AXS-07 and the applicability of our DCC platform to commercialization of that product candidate, I'm going to turn it over to Lori.

Hi, Joseph. So first let me just set the groundwork that part of the benefit of us being able to utilize the DCC platform is that we get the benefit of building this from scratch. A lot of companies due to the pandemic have had to retrofit their systems as well as their sales forces. So we're actually in a very good place as we think through the launches that are coming up and are purposely scaling this, making a platform that is scalable to our upcoming launches. If you noticed on the receptivity of remote detailing or virtual detailing, neuros are also extremely high. In fact, psychiatrists and neuros, typically, are in the top 3 of the ones that are most receptive to remote detailing.

We have a question from Vikram Purohit with Morgan Stanley.

This is Thomas Lavery for Vikram. Your release mentions that the IP portfolio for AXS-05 in depression has recently been expanded. Can you provide us with some color on the nature of these patent claims? And if possible, can you talk about how these patent claims expire in 2040 versus the prior patents in your portfolio that expire in 2035?

Great. Thank you for the question. What we're referring to are new patents that have been issued, which are more standard or more typical method of use patents for treating depression. And so those patents go out to -- several of those patents go out to 2040. In fact, I think at least one has issued. We've gotten a notice of allowance for more, and then we expect notices of allowance for even more than that. And so those could number a significant number of patents for that patent family. And the way that they differ from the prior patent families is, our prior patents, which go out to 2036, those were primarily pharmacokinetic patents. And what's nice about pharmacokinetic patents is -- one of the strong features of a pharmacokinetic patent is that it's agnostic to indication. So it covers all indications.

So we wanted to make sure that we have those patents first, which we do have. And then -- so this new family of patents around depression specifically are not pharmacokinetic patents. So those patents are -- the new patents are based upon the positive results that we have generated in our clinical trials thus far in our efficacy trials. So -- and by the way, this is by design to -- our strategy is to continue to expand our IP portfolio, and it's nice to see that not only is it broadly deepening, but also the runway is getting extended.

We have a question from Ram Selvaraju with H.C. Wainwright.

I think most of these are probably for Lori. I was wondering if you could comment on the current status of the commercial organization, how established it is at this juncture and at what stage you expect to be by the end of the year. And whether the kinetics of the establishment of the commercial organization are being impacted at all by the change in the time line for the NDA filing of AXS-05 in particular. I wouldn't imagine that that's the case, but just wanted to verify this.. And then I had a couple of additional follow-ups regarding the Veeva partnership, but maybe we can start there.

Hi, Ram. Thanks for the question. So the status of the commercial organization is we are actively building. As commercialization efforts ramp up, we are building to meet those efforts. We have a very strong team in place, one that I am extremely proud of, and we continue to hire at a very rapid pace.

What I can tell you about the impact of time line is, no, there are no changes due to the impact of time line. We are planning a very unique approach to launch that we -- there are a lot of activities and analysis being done to ensure that we are approaching the market in the right way.

Okay. Great. And then with respect to the Veeva partnership, maybe you can comment on 2 aspects that are particularly intriguing to me. Firstly, the way in which this relationship might potentially enable you to build a competitively privileged position from a commercialization standpoint relative to any potential competitor products, entities that might be counter detailing and so on. And then secondly, if you can comment on what specific products in Axsome's pipeline, particularly on a late-stage level, the Veeva relationship might be especially useful for or if you expect it to be pretty much equivalently useful for all of Axsome's product candidates.

Yes. So that's a great question. And so I'll answer your second one first. The -- as I mentioned in my previous comments, we are purposely building this in a scalable fashion. And I do think that with the approach that we are taking, where we are leveraging trends in the marketplace to be as effective as possible and building this infrastructure from scratch allows us to be highly efficient and flexible. And so the flexible piece is, I think, very important for us. We get to monitor and optimize our approach to the market, meaning, we get to monitor, as adoptions increases, how we intend to scale. And that would be applicable to both the AXS-07 launch as well as AXS-05.

In terms of how we think this will be beneficial to us in a competitive standpoint, as I mentioned before, most companies are having to retrofit their systems. And retrofitting systems is never easy because it's clunky and it increases opportunities for -- to be inefficient. And getting to do this from scratch, from the very beginning will allow us to have very efficient real-time dynamic ability to optimize our engagements with both patients and physicians.

Fantastic. Herriot, just a couple of questions on sequencing, if I may. Do you expect the meeting with the FDA with respect to the fibromyalgia indication to occur before or after the meeting with the FDA to discuss AXS-05 in smoking cessation? Which one do you expect to come first?

Fibromyalgia.

Okay. Great. And then with respect to the narcolepsy trial, can you give us a bit of color on how long you expect that trial to enroll for? What would you expect the time frame to be between start of enrollment and completion of enrollment?

It's premature for us to comment on the exact timing there. What we can do is just give you some parameters to maybe help you think about it. I think one determinant will be the size of the study. So once we launch the trial, and we'll provide details around sizing. As a reminder, though, what we saw in the Phase II trial was a very pronounced effect on cataplexy. So the study that we'll be conducting will have that as the primary endpoint. So that study was a crossover trial with roughly 20 patients. So if it were a parallel group trial, it would have been roughly a 40-patient trial. If you look at the package inserts for at least one other drug that has studied this level of impairment from cataplexy, the number of patients per arm was in the range of around 30-or-so patients per treatment arm. I'm not saying that, that will be the sizing of our trial because it will not be. That gives you kind of a sense.

And with regards to our CONCERT trial, so we were able to enroll that study in approximately 6 months with around 12 clinical trial sites. Again, this is not to say that this will translate directly into timing for our Phase III trial. But those are certainly metrics which are available, if you really search for them and which we certainly will be using to inform our time line projections, which we'll provide to you. We'll provide you some more information around that once we launch the trial in the first quarter.

Okay. And just as a follow-up to that. Do you expect to use any or all or some of the clinical sites that originally enrolled patients for CONCERT in this upcoming Phase III? Would that be a fair assumption?

That is a fair assumption that they would naturally be overlapping.

And the next question comes from Matt Kaplan at Ladenburg.

All right. Congrats, guys, on your progress during the quarter. Just wanted to follow up a little bit on the narcolepsy development plan. And specifically, I guess, with respect to -- beyond the clinical data from the COMET study and the planned Phase III additional study, what else do you need to complete to put yourself in a position to file the NDA?

Sure. So Matt, I think you led off with narcolepsy. I think you meant to say MDD in terms of -- and correct me if I'm wrong, but I think that that's your question in terms of what remains for that NDA filing, is that right?

Well, I want to follow up on both of them, but yes, both narcolepsy and MDD.

Okay. Sure. So starting with MDD, where the NDA -- pre-NDA submission activities, the major ones, are largely complete. So in terms of the clinical trials, for example, which would be rate-limiting, specifically the COMET long-term safety trial that we announced has been completed, and we'll have the results for the COMET sub-studies by the end of the year, and we'll announce those. So we're in great shape there in terms of things that need to be done from a patient perspective, from a patient data perspective. And now really, it's putting it all together and making sure that we have a quality submission package.

And then with regards to narcolepsy and what would be needed for an NDA filing there, so as you know, we did have a breakthrough therapy meeting with the FDA. Based upon the results of that meeting, we intend to conduct the one Phase III trial. And the one Phase III trial, along with a completed CONCERT Phase II trial, those will be used for the NDA filing.

Okay. And then maybe a question for Lori. With respect to your plans of utilizing the DCC approach, can you speak to other examples of companies or products that have been launched in a similar fashion or some of the components of what you're thinking about that have been successful in the past?

Sure. So we don't believe that there are any other companies using a platform such as this to launch. And that's part of why we think this is so important and also speaks to -- the trends in the marketplace are what's driving our decisions to do this. It's largely led by what's happening with the pandemic, but it's also forcing behavior changes that we believe are not going to change in terms of adoption of remote detailing that allows for convenience as well as efficiency for both companies as well as physicians.

There are several companies who have launched in a primarily remote fashion over the course of the pandemic period and have done so quite well. They have -- there have been instances where that approach worked very well. But again, what benefit we get is that we don't have to quickly pivot, meaning we don't have to take a sales force that was primarily prepared to be face-to-face and switch them to remote. We don't have to reintegrate systems that could be very clunky and complicated. We get to build it from scratch, and so we think this sets us up for a very efficient position.

We have a question from Joon Lee with Truist Securities.

This is Miguel on the line for Joon. Could you provide more specifics on what manufacturing data related to the MoSEIC platform will be added for AXS-07? Question is, what are the key discussion points with the upcoming meeting with the FDA regarding AXS-05 for smoking cessation? And what is the role of the new collaboration moving forward?

Great. So with regards to the additional manufacturing information, this is standard information when you manufacture additional batches. So we continue to manufacture additional batches of drug. And while we already have very long-term stability data on other batches, we think that because of the unique nature of the delivery technology, this can only help to make the submission robust and assure that there are no hiccups during review.

With regards to the AXS-05 in smoking cessation, what we're going to be looking for from that FDA meeting is guidance on the path forward to get the product approved. So -- and that is typically what we like to do early on in development with our product candidates is to get agreement, preliminarily with the agency, on various points of clinical development that give -- that would give us confidence to be able to move quickly once we have that information.

Typically, we would have gotten that information already, but with AXS-05 in smoking cessation, the development there was a little bit different because we did conduct that Phase II trial under a collaboration with Duke University. So but we're looking forward to this FDA meeting and to getting clarity on the path forward.

We have time for one more question that comes from Myles Minter with William Blair.

Maybe just one for Lori. I'm just wondering with the DCC commercial rollout, obviously, the initial focus will be to really talk to those neuropsychs and neurologists out there. But given the nature of the platform, have you had any considerations for primary care physicians and how they might be integrated into this program that a traditional sales force that you might implement cannot?

Myles, thanks for the questions. Absolutely. So part of our initial targeting, especially on AXS-05, will be for what we're calling mental health-focused PCPs. And there's a very large subset of those who are high prescribers. And so we will absolutely use this platform to try and increase that reach. But keep in mind that this is not just a remote detailing platform. We're looking to optimize all channels in how we reach physicians. So we do believe that there are ways to be effective with the PCP market that way.

Okay. And then maybe on the COMET study, are we only going to see relapse rates from these sub-studies that you're running under that umbrella? Or did every participant get a MADRS rating before and at exit of that study? And then maybe how you're thinking about relatively interpreting that data. I know the STAR*D is obviously out there. We see relapse rates within a 3- to 4-month period. Obviously, 300 patients at 6 months and 100 patients at a year is more than enough to see something there. Is that the most relevant data set for this particular population? Or are you more willing to leverage this or compare this to real-world prescribing data and what we're seeing in the clinic with SSRIs?

So with the COMET trial, what we'll be looking at is the response of patients in the study. We'll be looking at onset of action, so when do you start to see meaningful improvements from patients. And then we'll be following the patients out over time. So it will give us a sense of also persistence of effects. The -- you mentioned relapse. Typically, you would look at relapse if you -- by conducting a trial, which specifically looks at relapse. And those are of the randomized withdrawal study types of design. This is not that type of study. So -- but because patients are going to be treated, will have been treated over a 1-year period, we'll have plenty of information on persistence of effects.

I'll now turn the call over to our speakers for any closing comments or remarks.

Great. We're excited about the potential of our pipeline. This is an industry-leading CNS pipeline, and we're also excited about the potential to make meaningful changes in the lives of patients with our product candidates should we develop them successfully. We expect the next few months to be very busy with our planned NDA filings and our continued launch readiness activities. So we look forward to keeping you updated on our progress, and we'll speak to you during the next conference call. Thank you.

Thank you. That concludes the call. Everyone, you may now disconnect.