Axsome Therapeutics Inc (AXSM) 2020 Q4 法說會逐字稿

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, Mark Jacobson, Chief Operating Officer of Axsome Therapeutics. Please go ahead.

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 fourth quarter and full year 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, commercial plans; and possible intended use of cash and investment.

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 of Commercial and Business Development; Dr. Amanda Jones, Senior Vice President of Clinical Development; and Dr. Cedric O'Gorman, Senior Vice President of Medical Affairs. Herriot will first provide an overview of the company and then review recent development and upcoming milestones.

Following Herriot, Nick will review our financial results. We will then open the line for questions. And with that, I will turn the call over to Herriot.

Thank you, Mark. Good morning, everyone, and thank you all for joining Axsome Therapeutics' Fourth quarter and Full Year 2020 Financial Results and Business Update Conference Call. This past year was one of focused execution for Axsome, as we advanced our industry-leading CNS pipeline towards marketing application submissions.

Our portfolio comprises 4 late-stage product candidates under development for 6 distinct indications, representing unmet medical needs that affect over 60 million patients in the U.S. alone. Our focus this year will be on the regulatory activities surrounding our NDA filings for AXS-05 and AXS-07, launch readiness to ensure a successful transition to commercialization, assuming product approvals and continued advancement of the rest of our late-stage CNS pipeline.

I will provide a brief update on our pipeline and pre-commercial activities before turning it over to Nick, who will provide a financial update. Starting with our first lead product candidate, AXS-05. The New Drug application, or NDA, for AXS-05 for the treatment of MDD has been submitted. We intend to issue a press release following the FDA's decision regarding its acceptance of the filing. This NDA submission is a major milestone for the company as it brings us closer to potentially making this innovative treatment available to the millions of patients who are living with depression.

AXS-05 is a novel, oral and NDA receptor antagonist with multimodal activity. If approved, AXS-05 has the potential to be the first new oral mechanism of action for depression in over 60 years. In the fourth quarter, we announced positive results from the long-term open-label Phase III COMET trial, demonstrating rapid, substantial and durable improvements in depressive symptoms and functional impairment that was sustained over the 12-month treatment period with AXS-05.

AXS-05 was well tolerated with long-term treatment with a safety profile consistent with that observed in the previously reported controlled trials. We also announced positive results from the Phase II open-label COMET sub-studies in patients failing one prior treatment -- failing 2 prior treatments and in patients with suicidal ideation.

Moving on to our Alzheimer's disease agitation program with AXS-05. Alzheimer's disease agitation is a serious and debilitating condition for which there is currently no approved treatment. Last year, we announced positive results from the pivotal ADVANCE-1 trial, which demonstrated rapid and substantial improvement of agitation in patients with Alzheimer's disease with the AXS-05 treatment.

We subsequently received Breakthrough Therapy Designation for AXS-05 in this indication. In December, we launched our second pivotal trial, the ACCORD study, which is a double-blind, placebo-controlled, randomized withdrawal study.

Turning now to our migraine program with AXS-07. We are completing compilation of the NDA, which we expect to submit to the FDA early in the second quarter. There is a significant unmet need for more efficacious treatments for migraine. The World Health Organization ranks the disability from severe migraine attacks on par with that from dementia, quadriplegia or active psychosis. AXS-07's novel oral, multi-mechanistic approach may help to address this unmet need.

In the fourth quarter, we announced positive results from the long-term open-label MOVEMENT trial of AXS-07, demonstrating rapid, substantial and durable relief of migraine pain and associated symptoms over the 12-month treatment period. AXS-07 was well tolerated over long-term treatment with a safety profile consistent with that observed in the previously reported control trials.

Moving next to our AXS-12 product candidate for narcolepsy. Narcolepsy is a serious and debilitating condition with limited treatment options. Results from our Phase II trial demonstrated the potential for AXS-12 to address a broad range of narcolepsy symptoms. We expect to initiate a Phase III trial of AXS-12 in narcolepsy in the second quarter. While our AXS-14 product candidate for the treatment of fibromyalgia, we are scheduled to meet with the FDA in the second quarter of this year to discuss the development plan for this program.

AXS-14 has previously met the primary endpoint in a Phase III and in a Phase II trial for the treatment of fibromyalgia. Our intellectual property portfolio continues to grow with recently issued and allowed patents for AXS-05 and AXS-07. The number of issued U.S. patents for these product candidates now totaled 50 for each, with protection extending to 2040 and 2036, respectively.

With potential FDA decisions on 2 NDA filings over the coming year, preparations for potential commercial launch are well underway. All functional commercial leadership is in place, and the team continues to expand. Sales force structure and design have been finalized, and the hiring of sales managers and representatives will begin shortly. The infrastructure for our proprietary DCC, or Digital-Centric Commercialization platform is in place and payer engagement activities have started.

We are excited by the differentiated clinical profile of our numerous product candidates, the potential of our investigational medicines to deliver significant benefit to patients and our planned commercialization approach. I will now turn the call over to Nick, who will provide a financial update.

Thank you, Herriot, and good morning, everyone. Today, I will discuss our fourth quarter 2020 results and provide some financial guidance. We ended the fourth quarter with approximately $184 million in cash compared to roughly $202 million at the end of the third quarter, a net decrease of approximately $18 million.

R&D expenses were $17.4 million for the fourth quarter ended December 31, 2020, versus $19.2 million for the comparable period in 2019. The decrease of $1.8 million was driven by the completion of a majority of our clinical trials, which were ongoing in the comparable prior period, offset by costs related to the preparation of AXS-05 and AXS-07 NDA submission.

G&A expenses were $10.4 million for the quarter ended December 31, 2020, and $5.2 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. Net loss was $29.2 million or $0.78 loss per share for the quarter ended December 31, 2020, compared to a net loss of $24.8 million or $0.71 loss per share for the comparable period in 2019.

Net loss for the year ended December 31, 2020, was $102.9 million or a loss per share of $2.77 compared to a net loss of $68.3 million or $2.01 loss per share for the comparable period in 2019. As a reminder, in Q3 of 2020, we secured a $225 million term loan facility with Hercules Capital, of which $175 million in funding remains available. This committed non-dilutive capital gives us additional financial flexibility through the anticipated potential commercial launches.

We believe our current cash position of $184 million, along with the remaining 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 fourth 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) Your first question comes from Charles Duncan from Cantor Fitzgerald.

Congrats on the forward motion and progress with 05. I had a couple of quick questions. With regard to the label -- and I imagine you'll be talking about this more in terms of the claims that you were asking for with 05 NDA. I guess I'm wondering, would you anticipate the label to perhaps -- the approval label to be explicit regarding the COMET outcome or COMET results with 1 and 2 failures and suicidal ideation? Or would that just be data included in the label and it would be a generalized MDD approval, if granted?

So the label that we are targeting and that we have submitted the NDA for is the treatment of major depressive disorder, MDD. And the -- now our clinical trials or our control clinical trials as well as our open-label long-term studies do include a broad range of patients who have MDD. And so the -- we would not expect specific indications, for example, suicidal ideation to be in the label.

However, patients with MDD do have suicidal ideation and patients with MDD have been treated with more than one prior treatment. So those data from a COMET trial, they have been included in the NDA submission. Those are data which certainly will be published, and which we think will be very useful to clinicians, and we'll be able to make those data available to clinicians using our medical find [sales line] functions.

Okay. That makes sense, should be useful for prescribers. Just sticking with 05, one last quick question. Regarding the ACCORD study in Alzheimer’s agitation, can you provide any additional color on how that study is going in terms of enrollment? And what you anticipate the, call it, screen failure rate to be or the number of patients enrolled versus going on to the, I guess, the blinded portion and then being withdrawn?

Those are great questions. It's early days in the study. So we launched the trial at the end of December, as you know. So it's very early days, especially for this type of study, whereby you do have this lead in where everyone is treated with AXS-05 in an open-label fashion, and then they'll monitor, not just for response, but for stable response prior to randomization.

We'll have more to tell you, and we'll be happy to share some of those observations and incorporate them into any kind of timing update with regards to the trial. But right now, it's too early.

Okay. Last question regarding commercial. You mentioned the sales force sizing had them finalized, and I guess, I'm wondering what you anticipate that sizing to be roughly, not specifically? And then the breakdown of psych versus neuro focus? And how do you plan to accomplish that?

I'm going to turn it over to Lori.

I think you probably will not be surprised if we tell you we're not going to tell you the exact size of the sales force, but what I can tell you is that we are highly confident that the size that we have anticipated will cover the amount of physicians that will be high prescribers of AXS-05, and we do believe that our Digital-Centric Commercialization approach will be able to provide information to physicians when they need it, how they want it and the time that they want it.

And I think that's really important to understand because our promotion is not just personal. There will be a large component of non-personal promotion as well. And regarding your question around 07 and that launch, look, everything we're doing in preparation for the 05 launch is working under the assumption that 07 will follow very closely after. So all the structures that we're putting in place, sales force, digital will all be readily capable of scaling at the time of launch for 07.

Your next question will come from Marc Goodman from SVB Leerink.

I understand you're not going to give us the number of reps, but can you give us sense of the spend that you're going to do this year, maybe some type of spending guidance, specifically for SG&A is what I was focused on? Second, can you just give us a sense of the payer discussion so far for depression and how those are going? And how they are appreciating the differentiation in the new mechanism? Just curious how that's going.

And then third just curious on the fibromyalgia, you're going to meet with FDA. Can you talk about the different scenarios, if they come back and say, okay, you can file with what you have, are you prepared to file and then move forward and market this product on your own? Are you thinking about potentially partnering it just because it's such a large indication? And if they say, do another study, are you prepared to start another study before the end of the year?

So I'll take the fibromyalgia question first, and then I'll turn it over to Nick and then to Lori for the other questions on spend and payer discussions. With regards to fibromyalgia, we're looking forward to our FDA meeting, which is scheduled in the second quarter to discuss the development path forward for that product candidate. This will be our first meeting with the FDA since we've gotten the data. So we'll have a lot more to tell you, hopefully, once we have that meeting.

As a reminder, there are 2 studies, 2 efficacy trials and control trials, which have been completed and which were positive. So that puts us in a very good position. In the theoretical -- under the theoretical scenario where, let's say, there's absolutely nothing more that we had to do from a clinical perspective. We would still need to manufacture commercial supplies.

And what I can tell you is that work is already underway to make sure that we can manufacture the product. This is a novel chemical entity. And so therefore, there's been a lot of work that our CFT team has been doing in order to synthesize it. So that work is well underway and is progressing well. I'll turn it over to Nick to answer your first question.

Marc, as you know, we don't give necessarily expense guidance. I can give a little bit of guidance on the cash runway. As a reminder, we had $184 million in cash at year-end. We additionally have the $225 million debt facility. So we feel like we're in a really strong position from our financial resource base. The cash runway, so you're aware, this takes us into at least 2024 based on our current operating plan and includes all launch readiness, all launch expenses, including field force for AXS-05 and AXS-07.

Also includes funding for the second Phase III Alzheimer's agitation trial, continuation of the MERIT trial for TRD and soon to be started AXS-12 trial in narcolepsy. So the runway currently, just in conclusion, takes us through both potential launches upon NDA approval for both MDD as well as the acute treatment of migraine.

And I'll quickly answer the payer question. So I think we all know depression is the number one cause of disability worldwide. And the prevalence of depression is continuing to grow, especially with the pandemic. Sometimes we heard to the tune of 3x. So payers are paying attention, right? And depressed patients cost money, and they are acutely aware of the other clinical profiles of products that are already on the market.

When we discussed with payers and what we've seen in early discussions, yes, bringing forth a novel mechanism of action that's patient-friendly and reminding them that this will be the first one in 60 years. It's interesting to them, very interesting to them. But what really sticks out is our clinical profile. So our data is highly differentiated versus the other products on the market. And what I believe we've heard again and again, in early discussions, what attracts them most is the rapid onset of remission and the durability that we show with products.

And your next question comes from Joon Lee from Truist Securities.

So following up on the payer discussion and you mentioned the rise and prevalence of depression, I wanted to follow-up on that. In one of your slides, you noted increase in the prevalence of depression from 22 million pre-pandemic to 71 million during the pandemic, more than 3x increase in prevalence. Unfortunately, you've already completed your Phase III. But if you were to conduct a Phase III trial today, would you do anything differently?

What I'm trying to understand is, is that new cases of depression during the pandemic are bonafide MDD or something more multifactorial in nature. And if you would have needed to upsize the study or something like that to suppress noise? And is this phenomenon unique to the U.S. or similar in other countries? Maybe -- just love to hear your thoughts there.

Thank you for the question. A lot of theoreticals there. But would you -- I think you do raise some interesting questions. So from a public health perspective, it's very clear the effect of the pandemic on mental health and also on depression symptoms. It's been very well documented, I think, definitely in some high-profile journals by some well-respected clinicians.

So the data are clear. There is a significant increase in depression symptoms. And Lori can maybe speak to this a little bit, but we started to also see that work its way into prescription trends.

Now -- so what that means is there's acute need to treat patients. And also, there's a great opportunity for companies that can provide novel mechanisms of action, but we'll work quickly that will help these patients. So that's on the clinical need side of things. Now from a clinical trial conduct perspective, I think you do bring up an interesting point that there is an unknown there.

And that unknown is what impact with the pandemic and with the mental illness from a pandemic have potentially on being able to test your drug to see if it works. That is theoretical. And we -- so we can't really say too much about that. One of the things that we did do was to look at the impact of AXS-05 during the pandemic through our long-term open-label safety extension trial. And so we were very interested to see what impact our drug would have on patients on their depressive symptoms in the context of the pandemic.

And we can only speak to our data and what we showed, as you know, and what we reported was a very profound reductions in depressive symptoms incredibly high rates of response and remission that either will maintain or increase over the 12-month treatment period.

Your next question comes Joseph Thome from Cowen and Company.

A little bit on the COMET data. In those subset data, was there anything that surprised you in terms of response in any of the individual subsets? And maybe in terms of positioning upon launch, is there anything that your MSL team is doing to position the therapy in a certain subset of patients that would be maybe more early adopters?

And then finally, related to that, does the subset data give you any read-through into your expectations for MERIT later this year?

In terms of points that were surprising in the data, I think we -- it was good to see that the rapid onset of action and the significant percentage of the patients achieving remission and response that we saw in the control trials were replicated in the COMET data. One of the substudies that we're really interested in was the suicidal ideation substudy. Small number of patients, but as you can imagine, rapid onset of action is really important for that symptom and in those patients. And what we saw was that there was a resolution of suicidal ideation in that subgroup in 60% of the patients at week 1. And that only increased to the vast majority of patients after 2 weeks. So that was definitely interesting.

And I think number two on the list was the fact that the efficacy that we saw in the controlled trials did translate also to patients who had the failed 2 prior treatments. So patients who are traditionally referred to as treatment-resistant depression patients. So it was really good to see that in a real-world setting.

As it relates to expectations, as it relates to what implications that would have for the MERIT study, those points -- those observations can only be positive in terms of the profile of the product, and we've never done a randomized withdrawal study design before. So it'll be interesting to see what those show and that's the benefit and one of the reasons why we conduct Phase II trial. So we're looking forward to seeing how the product performs in that setting. And then I'm going to turn it over to Cedric to talk about MSL strategies.

Yes, thanks, Herriot. I would just say that these data from COMET are very exciting. I mean, in terms of response on MADRS, remission on MADRS and also fact that it translates into clinically observable response and remission rates, and this was clear across the overall COMET as well as those who had failed to respond to antidepressants in the current episode had suicidal ideation. So the MSLs have these data in hand. We've been out talking to key opinion leaders, getting their insights on the data that's been a great impressive activity to it and excitement about the new mechanism of action.

And I think that what's important from COMET is not only are you seeing these responses early on but they're being sustained and with really sort of impressive compliance and maintenance with treatment up to 12 months. So that's what's really exciting is that the drug appears to be working, but also patients are willing to stay on it over the long term. So the MSLs are out there right now, getting insights and talking about these data, and we'll be presenting data at upcoming conferences as well.

Your next question will come from Myles Minter from William Blair.

I'm just wondering from the payer perspective, whether you've sort of engaged in the conversations regarding where 05 might actually sit in the treatment paradigm from their perspective? And whether the DCC platform that you're running on the commercial front, whether that's actually touching base with the appropriate prescribing physicians that are seeing patients say with like 2 or more prior failed antidepressants?

Myles, I think it's a little bit too early for us to know where the payer discussions are going to net out. So answering your first question, difficult at this time. We do -- as I mentioned earlier, we are very encouraged by those discussions that we are having right now. They seem to respond very well to our clinical data package that we're putting in front of them.

In terms of the DCC approach, I'm not quite sure I understand or I understood your question correctly. Could you repeat it? Would you mind repeating it?

Yes. I'm just wondering, like -- with the target prescribing accounts for that platform and also for your sales force, what the breakdown of patients that have failed 2 or more prior therapies would be at those target accounts and better classified as TRD patients versus standard MDD?

I think I understand your question. Yes, so I'll turn it back to Lori, but I just wanted to just point out that the data are pretty clear that roughly 2/3 or more of patients already failed or responding adequately to at least one prior treatment.

Yes. I agree, the majority of our target physicians are high-prescribing physicians. So the likelihood that they're treating patients who have failed one or more is really high.

Okay. Cool. And then maybe on 07 and the MOVEMENT trial data looks really good from my perspective. Could you give any update as to the frequency of dosing for patients out to 12 months? And also were those patients treated at the earlier signs of migraine like in INTERCEPT or at confirmed migraine like in MOMENTUM?

Myles, I want to turn it over to Amanda.

For the MOVEMENT study, the patients were allowed to treat their -- at any point in time following the onset of migraine pain. So it really reflects more the real world data and real world use of the drug and also the data that was captured during the MOMENTUM and INTERCEPT trial.

Your next question will come from Vamil Divan from Mizuho.

This is (inaudible) for Vamil. Just a couple of questions. On AXS-07, just wondering why the push back to 2Q earnings -- on 2Qs filing, what is the same issue that was as previously discussed or something that's different? And secondly, on -- just thinking about pricing ahead, just wondering how you're thinking about pricing for AXS-05 in MDD, but you will also have [attrition] and the pricing there could be different? I'm just wondering how you're approaching this? And how your, I guess, discussion with payers might be going?

With regards to 07 and the NDA filing, the team remains on track to complete the filing by the end of the quarter. However, we are waiting on one vendor report, which will slip into the very beginning of the second quarter, and that's the reason behind the adjustments there in guidance. And, Lori?

Regarding pricing, so whenever you approach pricing discussions with payers typically, companies focused on fair and timely access, and a large portion of that will be associated with where you price. But the balance of that is we need to price for the value that the product brings. And so we're working through that right now to make sure that we understand how we appropriately price to represent what value we're bringing to the market.

And then Lori just go through our safety AD agitation.

Yes, and that encompasses the AD agitation fees as well.

Your next question will come from Matt Kaplan from Ladenburg Thalmann.

I want to congratulate you on the progress during the quarter. Can you give us a sense now that you've submitted the AXS-05 to the NDA. I guess, given the Breakthrough Designation you have in MDD, what are your expectations for a potential priority review?

So as you mentioned, we do have Breakthrough Therapy Designation for the product. And we do believe that we qualify for priority review, which is 6 months review. However, that is a determination, which is made by the FDA. And the way that it works is that priority review is not automatic. At the time of the NDA filing, you do request priority review. And it is a determination, which is made and communicated to the company upon the FDA decision of whether or not to file the application.

So our plans with regards to launch, et cetera, they're predicated, they assume a 6-month review. But again, that is really up to the FDA.

Okay. Helpful. And then in terms of AXS-07, I guess, we focused a bit on the commercial prep on 05 already. But I guess, maybe more for Lori, what -- where are you in the preparation in terms of research you're doing and payer interaction for 07 given, I guess, it's kind of the near-term NDA filing there?

Regarding 07, as I mentioned earlier, we have always anticipated that 07 would follow very closely behind 05 in terms of launch. And therefore, we've actually been preparing on all fronts to have a staggered approach, but scalable if we were to receive approval for AXS-07.

In terms of payer negotiations, exactly, we have performed market research, but have not started the 07 payer discussions just yet.

Okay. Very good. And then last question in terms of, Herriot, you mentioned you're on track to start the Phase III for AXS-12 in narcolepsy, cataplexy next quarter. Can you give us a sense of what your thinking is in terms of the design of that trial and, kind of, time line to completion potentially?

So with regards to the trial design, it will be a parallel group design. So it will be similar in some ways to the Phase II trial, which we conducted, except the Phase II trial was a crossover design. This will be a parallel group design. So we expect -- we would expect to randomized subjects to AXS-12 and into placebo.

And then with regards to expectations around how long it would take to enroll the study. Once we start the study, we'll provide you details with regards to the size of the study. And that, of course, will determine potentially how fast it could enroll.

One of the things that we can point to are the metrics around the Phase II enrollment. As a reminder, that was a 21-patient study, which was conducted at roughly 12 sites. And that enrolled in approximately 6 months.

Your next question will come from Vikram Purohit from Morgan Stanley.

Great. Just had one on AXS-05 for smoking cessation. So I've seen your release that you have an FDA meeting scheduled here for the third quarter. I just wanted to see where you're looking to learn from a meeting with the FDA here? And what you think an eventual subsequent pivotal study in this indication could look like?

We're very excited about smoking cessation. And on the back of the positive of Phase II data from a small study, we're looking to meet with the FDA to figure out what an efficacy trial would look like. So the Phase II study did look at smoking behavior, but that is not a registration endpoint. Certainly, it was very helpful for signal detection, which we saw.

And the -- so what we're going to be looking to get out of that meeting is guidance and agreement on the design of the next study, which would be an efficacy trial. So we're very much looking forward to those discussions. Registration trials in smoking cessation, typically, the endpoint is abstinence. So that is what we would expect for the next study.

And your next question will come from Chris Howerton from Jefferies.

So I guess, most of it have been asked at this point. But I guess for 05 with respect to Alzheimer's disease agitation, there's a possibility that we're going to get increased competition within that space over the next couple of years with a variety of companies developing therapeutic there. So I guess, how is it that you see 05 competing in this landscape, particularly, obviously, as we all know, safety is the key concern for this patient population?

It's a very interesting and serious disease area. The term on that medical need gets thrown around quite a bit. But here, this would be a good

A good description.

Yes, it'd be -- yes. So you're talking about the disease where there currently is no product that is approved and the drugs that they're used off label have Black Box warning against their use in that specific patient population. And yet clinicians do need to treat these patients because of the seriousness of the condition.

So right now, there's nothing approved, so from a competitive perspective. So it really all depends on the clinical data. It's very difficult for us to comment on drugs that are in development. We know that this is an area that has not been kind to drug development. And we're very fortunate that we have one pivotal trial that is positive that did show really good efficacy, which was rapid, but also really good safety.

So the drug is incredibly well tolerated in the ADVANCE-1 trial. And so we're looking forward to enrolling and completing the ACCORD study. So and with regards to just further to other products that are in development, one thing that I would say is that it shows that there is a significant clinical need. And it'd be great to have numerous products that are available to treat these patients, given the seriousness of the condition. But it's impossible to comment on theoreticals when we have not seen positive data from other companies.

Your next question will come from Yatin Suneja from Guggenheim.

This is Eddie on for Yatin. Just a follow-up on TRD. Can you -- given what you saw in STRIDE and then recently with the COMET study, can you give us an update on sort of what the development path looks like and the time lines to get to an sNDA in TRD? And how will the MERIT data coming later this year influence that path?

The indication that we filed is MDD, and so that's the broadest indication. So that encompasses the entire spectrum of major depressive disorder. So we're very happy with that indication should we be successful with the NDA review. And we do not intend to conduct another Phase III trial in treatment-resistant depression. What we have done and is to generate data that will help clinicians to understand how the product performs in a wide range of patients with major depressive disorder, including patients who failed 2 prior treatments.

So from that perspective, we're very happy that the STRIDE study was conducted. We think the COMET TRD data does provide very helpful information to clinicians in a real-world perspective. And we think that the MERIT study may also provide data that will be useful to clinicians, again, in the right setting, that is in a scientific setting.

We have time for just a few more questions and we'll try to get through as many as possible. Your next question is from Rag Selvaraju from H.C. Wainwright.

And I wanted to ask about the general allocation of sales and marketing, commercialization resources across the different indications for AXS-05 as you look towards the possibility of this drug potentially being triple or even a potential quadruple threat in the CNS neurosite space. And in particular, if you could talk through how you anticipate the different sales and marketing strategies to be taken with AXS-05 effectively being deployed?

And if you can especially describe any particular initiatives that are likely to be aimed at specific types of institutions with the aim of optimizing the commercial value of this product?

Thanks, Ram, for the question. I'll turn it over to Lori. But you do raise some interesting questions, which we've certainly thought about as a team with regards to the potential different indications for AXS-05.

It's a little bit difficult question to answer at this point in time. AD agitation, we need to see how the trial finalizes, but we are absolutely always thinking about how we leverage the sales force, when we leverage the sales force, and what that overlap of physicians might look like.

Again, as we built our sales force sizing and design and structure, we did that with the understanding that we would have follow-on indications coming in -- particularly in different disease areas and also different treating physicians. So we've taken great efforts to ensure that there's efficiency there, if that were to happen.

So -- and specifically, with respect to the smoking cessation indication, are you looking at that as being primarily an indication where the principal commercialization thrust would be through advertising as opposed to boots on the ground relative to, for example, MDD or Alzheimer's associated agitation? Or are you thinking about it in terms of a situation where you might need to field a totally separate sales force in order to potentially market AXS-05 in that indication as well?

Yes, Ram, it's premature for us to talk about marketing for smoking cessation. So let's first conduct the trials and see what the profile is. And -- but those would be great questions and great problems to have which we would certainly solve should we have positive data.

Okay. And then I was just wondering, I know that you haven't had the actual meeting discussion yet on the fibromyalgia candidate. But have you received any indication one way or another as to whether the FDA considers the current efficacy data package to be adequate? Or if they are looking for you to conduct an entire additional registrational program aimed at adding to the efficacy data package for assembling a potentially fileable, approvable application in fibromyalgia?

We've not met with the FDA, and we're not going to speculate on what the outcomes of those discussions might be. But we're very much looking forward to sitting down with them and discussing what we viewed to be the unique data in this area, which is still an area of high unmet medical need. As a reminder, there are only 3 approved products to treat fibromyalgia. It is a condition that have a variety of symptoms. Many of which are not addressed by the small numbers of currently available treatments.

Okay. And then lastly, just a housekeeping item on stock-based comp. How are you anticipating stock-based comp to trend this year relative to last year? And looking at your upcoming hiring plans, and in particular, sales and marketing infrastructure build-out? Should we expect a significant increase in stock-based comp expense for 2021 relative to 2020?

Ram, it's Nick Pizzie. Yes, I can answer that question. So we did have an increase in stock-based comp year-over-year, and that's just correlated, obviously, to our stock price, specifically this year. And as we build a field force and continue to ramp up other functions, you would continue to expect an increase in stock-based comp and obviously dependent on where our share price is based on the Black-Scholes calculation when we do that. So -- and it is amortized over a 4-year period typically for our stock-based comp. So it wouldn't be all in 1 year when we have an impact from the sales force.

Your next question will come from Ashwani Verma from Bank of America.

I just had one. So in terms of the AXS-05 patent, just trying to figure out how many of these 50 plus patents that you have cited can be listed on the Orange book? My understanding is that as a new NDA, you'll have to file the Form 3542 and list the patents that pertain to the specific attributes of the drug for the MDD label in this situation. So just curious how many of the patents would meet that criteria?

Ashwani, as a reminder, we have approximately 50 or more than 50 patents in the U.S. covering AXS-05. And the vast majority of those patents are Orange book listable. And the other point to mention is that most of those patents provided protection out to 2034. The more recent ones provided protection out to 2040. And in addition, the new patents encompass different families of patents. So not only do we have a pharmacokinetic patents but we also have method of treating disease patents. Furthermore, we would expect that the patent families would continue to expand.

Got it. And just to follow-up, like, have you filed that formulation patent that you talked about earlier?

So the -- I'm not certain of which formulation patent you're referring -- are you referring to a particular patent? Typically, what we do is, is we do talk about patents that have issued. We do have some claims around our formulation specifically. So some of the new patents that have issued specifically speak to our formulation as well as a method of treating a disease. And I think what I was referring to is additional patent families, which we would expect to file in the future so to further expand the patent portfolio.

Your next question will come from David Hoang from SMBC.

So just a quick couple. You talked about the Digital-Centric approach to the sales force and the launch. And I'm just curious as to what gives you confidence that, that type of approach, detailing physicians in that way would be successful versus a more traditional in-person effort by the sales force?

David, thanks for the question. Yes, we have high confidence, mostly based on data. We do know that psychiatrists and neurologists are 2 of the highest adopters of remote detailing. In fact, a lot of psychiatrists, we know actually prefer it. Psychiatrists actually trend anywhere from 60% to 70% of their details are remote, and that's recent data. And that was actually higher than data even 6 months ago when the pandemic was actually much more prevalent.

So we feel pretty confident that this is a sound approach. And we certainly are not alone in this. Most companies are doing this, and physicians right now are currently dictating how they want to see sales reps. So they will tell you if they want you to come in in-person or they want you to come in via remote detail, and we're going to use data analytics to make sure that we're approaching them correctly.

Okay. Great. That's really helpful. And then just on 05 in Alzheimer's agitation. Just wondering about the environment for usage there. Do you envision that the drug would be mostly something for the home in the community setting? Or would you also expect to see sort of a large uptake in the long-term care setting?

So our studies were -- well, we conducted one trial, so our pivotal trial and also just our currently ongoing study is -- or were conducted in patients who were based in the community. And we did that for a lot of reasons. And then -- so -- but there is no reason to believe that the drug would not work in any setting.

And the reason why we focused on community-only patients is, one, you want to prevent patients from actually being institutionalized. So if you can treat them, you want to keep them out of the hospital and out of nursing homes. And so -- and however, once you show that the product works, so we -- there's no reason to think that the pharmacology is going to change depending on the setting.

We have no further questions in queue. I turn the call back over to the presenters for closing remarks.

Well, thank you all for joining us on the call today. This year will be an important one for Axsome as we move closer to potential commercialization on our product candidates. We look forward to keeping you updated on our progress.

Thank you, everyone. This will conclude today's conference call. You can now disconnect.