Axsome Therapeutics Inc

NASDAQ:AXSM

Earnings Call Transcript 2020-Q4

[Operator]

Good morning. And welcome to the Axsome Therapeutics Conference Call. Currently, all participants are in a listen-only mode. Later there will be a question-and-answer session and instructions will follow at that time. As a reminder, today's conference call is being recorded.

I would now like to turn the conference over to your host, Mark Jacobson, Chief Operating Officer at Axsome Therapeutics. Please go ahead.

[Mark Jacobson, Chief Operating Officer]

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 non-clinical plans, our plans to present or report additional data, the anticipated conduct in the source of future clinical trials, regulatory plans, future research and development plans, commercial plans and possible intended use of cash and investments.

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are 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 and 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 developments 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.

[Herriot Tabuteau, Chief Executive Officer]

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 the focused execution for Axsome as we advanced our industry leading CNS pipeline towards marketing, application, submissions. Our portfolio comprises four late stage product candidates underdevelopment for six 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 advancements of the rest of the 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 of NDA for AXS-05 for the treatment of MDD has been submitted. We intent to issue a press release following the FDA’s decision regarding acceptance of the filing. The NDA submission is a major milestone for the company and it brings us closer to potentially making this innovative treatment available to the million of patients who are living with depression. AXS-05 is novel, oral and NMDA 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 3 COMET trial demonstrating rapid, substantial global in depressive symptoms and functional impairment that will sustain over the 12 month treatment period with AXS-05.

AXS-05 was well tolerated with long term treatment with the safety profile consistent with that observed in the previously reported controlled trials. We also announced positive results from phase 2 open-label COMET sub studies in patients failing one prior treatment, failing two 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 a pivotal ADVANCE-1 which demonstrated rapid and substantial improvement of agitation in patient with Alzheimer's disease with AXS-05 treatment.

We subsequently received breakthrough therapy designation for AXS-05 in its 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 all 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 treatment for migraine. 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 long-term open-label moment trial AXS-07 demonstrating rapid, substantial and global relief of migraine pain and associated symptoms over the 12 months treatment period. The AXS-07 was well-tolerated over long-term treatment with the safety profile consistent with that observed in the previously reported controlled 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 2 trial demonstrated the potential for AXS-12 to address a broad range of narcolepsy symptoms. We expect to initiate a phase 3 trial of AXS-12 in narcolepsy in the second quarter. While 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 phase 3 and a phase 2 trial for the treatment of fibromyalgia.

Our intellectual property portfolio continues to grow with recently issued and allow patents for AXS-05 and AXS-07. The number of issued U.S. patents for each product candidate now total 50 for each with protection extended to 2040 and 226 respectively.

With potentially FDA decisions on two NDA filings over the coming year preparation for potential commercial launch are well underway. All functional commercial leadership is in place and the team continues to expand. Sales for structure and design have been finalized. The hiring of sales managers representatives will begin shortly. The infrastructure for our proprietary DCC or Digital Centric Commercialization platform is in place. And peer 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.

[Nick Pizzie, Chief Financial Officer]

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 a comparable prior period offset by costs related to the preparation of AXS-05 and AXS-05 NDA submissions. 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 non-cash 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 for 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 turn loan facility with Hercules Capital of which $175 million in funding remains available. This committed, non-diluted 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 in 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.

[Mark Jacobson, Chief Operating Officer]

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

[Operator]

Thank you very much. [Operator Instructions] Your first question comes from Charles Duncan from Cantor Fitzgerald. Your line is open.

[Charles Duncan, Cantor Fitzgerald]

Hey, good morning Herriot and team thanks for taking our questions. Yes, busy time for you congrats on the forward motion and progress with 05. I had a couple of quick question. With regards to the label and I imagine you'll be talking about this more in terms of the claims that you were asking for was 05 NDA. I guess I'm wondering would you anticipate the label to perhaps approve label to be explicit regarding the comment outcome or comment results with one and two failures in suicidal ideation or would that just be data included in the label and it would be a generalized MDD approval if it’s granted?

[Herriot Tabuteau, Chief Executive Officer]

Good morning Charles and thanks for the question. So the label that we are targeting and that we have submitted the NDA for is the treatment of major depressive disorder MDD and now our clinical trials, our controlled clinical trials as well as our open label long-term studies do include a broad range of patients who have MDD and so we would not expect specific indications for example suicidal ideation to be in the label and however the patients with MDD do have suicidal ideation and patients with MDD have been treated with more than one prior treatment. So those data from the common trial that have been included in the NDA submissions those are data which certainly will be published and which we think will be very useful to the clinicians and will be able to make those data available to clinicians using our medical fines on functions.

[Charles Duncan, Cantor Fitzgerald]

Okay. That makes sense. It would be useful for prescribers just sticking with 051 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 of I guess the blinded portion and then being withdrawn?

[Herriot Tabuteau, Chief Executive Officer]

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 title study whereby you have this lead-in where everyone is treated with AXS-05 in an open-label fashion and then they're monitored not just for response but for stable response prior to randomization. We will have more to tell you and we'll be happy to share some of those observations and incorporate them into any kind of timing updates with regards to the trial but right now it's too early.

[Charles Duncan, Cantor Fitzgerald]

Okay. Last question regarding commercial, you mentioned the salesforce sizing had been finalized and I guess I'm wondering what do 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?

[Herriot Tabuteau, Chief Executive Officer]

Thanks Charles for the question. I'm going to turn it over to Lori.

[Lori Englebert]

Hey Charles thanks for the question. I think you probably will not be surprised if we tell you we're not going to tell you the exact size of the salesforce 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 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 of the structures that we're putting into place, salesforce, digital will all be readily capable of scaling at the time of launch for 07.

[Charles Duncan, Cantor Fitzgerald]

Okay. That's helpful. Thanks Lori and Herriot for the added color. Should be effective looking forward to the progress this year.

[Herriot Tabuteau, Chief Executive Officer]

Thank you.

[Operator]

Your next question will come from Marc Goodman from SVB Leerink. Your line is open.

[Marc Goodman, SVB Leerink]

Yes. Good morning. I understand you're not going to give us the number of reps but can you give us a 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 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 prepare to start another study before the end of the year? Thanks.

[Herriot Tabuteau, Chief Executive Officer]

Thanks for the multi-part questions there. 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 player 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. Now as a reminder there are two studies, two efficacy trials for quick 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 CFC team has been doing in order to synthesize it. So that work is well underway and is progressing well. I will turn it over to Nick to answer your first question.

[Nick Pizzie, Chief Financial Officer]

Thanks Herriot. Thanks Marc for the question. 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 $245 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 20-24 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 3 Alzheimer's agitation trial a continuation of the MERIT trial for TRD and the 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 treatment of migraine.

[Lori Englebert]

Hey and I will quickly answer the payer questions. So I think we all know depression is the number one cause of disability worldwide and the prevalence of depression is just continuing to grow especially with the pandemic, sometimes we've heard to the tune of 3x. So payers are paying attention. Depressed patients cost money and they are acutely aware of the other clinical profiles of products that are already on the market. When we discuss 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 and again in early discussions what attracts them most is the rapid onset of remission and the durability that we show with the product.

[Operator]

And your next question comes from Joon Lee with Truist Securities. Your line is open.

[Joon Lee, Truist Securities]

Hi, thanks for taking our questions and thanks for the updates. So following up on the payer discussion and your mention of rise and prevalence of depression, wanted to follow from that. In one of your slides increase in the prevalence depression from 22 million pre-pandemic to 71 million during the pandemic more than 3x increase in [indiscernible] unfortunately you've already completed your phase 3 but if you were to conduct a phase 3 trial to-date, would you do anything differently? What I'm trying to understand is if the new cases of depression during the pandemic are bona fide MDD or something more multifactorial in nature and if you would have needed to upside the study or something like that to suppress millions and there's this phenomenon unique to the U.S. or similar in other countries maybe just would love to hear your thoughts there. Thank you.

[Herriot Tabuteau, Chief Executive Officer]

Thanks Joon for the question. A lot of theoreticals there but 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 depressive 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 depressive 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 that will work quickly that will help these patients. So that's on the clinical needs side of things.

Now from a clinical trial conduct perspective, I think that that you do bring up an interesting point that there is an unknown there and that unknown is what impact would the pandemic and would the mental illness from a pandemic have potentially on being able to test your drug to see if it works. That's a theoretical and 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 is as you know and what were reported was very profound reductions in depressive symptoms. Incredibly high rates of response and remission that either were maintained or increased over the 12-month treatment period.

[Joon Lee, Truist Securities]

Fantastic. Thank you.

[Operator]

And your next question comes from Joseph Thome from Cowen & Company. Your line is open.

[Joseph Thome, Cowen & Company]

Hi there thank you for taking my questions. A little bit on the COMET data. In those types of 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 where anything your MSL team is doing to position the therapy in a certain subset of patients that will 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?

[Herriot Tabuteau, Chief Executive Officer]

So thanks for the question. In terms of points that were surprising in the data, I think it was good to see that the rapid onset of action and the significant percentages of patients achieving remission and response that we saw in the control trials were replicated in the COMET data. One of the sub studies that we were really interested in was the suicidal ideation sub study; a 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 one and that only increased to the vast majority of patients after two 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 two 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 you conduct phase 2 trials 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?

[Cedric O'Gorman, Senior Vice President, Medical Affairs]

Yes. Thanks Herriot. I would just say that these data from COMET are very exciting I mean in terms of response on [mattress] remission on that [mattress] and also the fact that it translates into clinically observable response and remission rates and this was clear across the overall COMET as well as those who have failed to respond to antidepressants in the current episode on suicide litigation.

So the MSL have these data in hand. We've been out talking to key opinion leaders getting their insights on the data has been a great progressive productivity 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 and 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.

[Joseph Thome, Cowen & Company]

Excellent. Thank you so much.

[Operator]

Your next question will come from Myles Minter from William Blair. Your line is open.

[Myles Minter, William Blair]

Hey everyone. Thanks for taking the questions. 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 two or more prior failed antidepressants?

[Lori Englebert]

Hey Miles, thanks for the question. 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 is 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 understood your question correctly. Could you repeat it? Would you mind repeating it?

[Myles Minter, William Blair]

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

[Herriot Tabuteau, Chief Executive Officer]

Yes. I think I understand your question. So I'll turn it over, I'll turn it back to Lori but I just wanted to just point out that the data are pretty clear that roughly two-thirds or more of patients already fail or respond inadequately to at least one prior treatment.

[Lori Englebert]

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.

[Myles Minter, William Blair]

Okay. Cool and then maybe on 07 and then the MOMENT trial data looks really good from my perspective. If you're giving any updates as to the frequency of dosing for patients out to 12 months and also were those patients treated at the earliest signs of migraine like an interceptor at confirmed migraine like in MOMENTUM?

[Herriot Tabuteau, Chief Executive Officer]

Hi Myles. Thanks for the question and study the patients were allowed to treat at any point in time following the onset of migraine pain. So it really reflects more of the real world data and real world use of the drug and also the data that was captured during the MOMENTUM and INTERCEPT trial.

[Myles Minter, William Blair]

Okay. Thanks for the questions.

[Operator]

Your next question will come from [indiscernible]. Your line is open.

[Unidentified Analyst]

Hey guys thanks for [indiscernible]. just want a couple of questions. On AXS-07 just wondering why the push back to 2Q earnings and 2Q's filing, most previously discussed or soemthing that's different and secondly, on just thinking about pricing ahead just wondering how thinking about pricing ahead just wondering how you’re thinking about price [indiscernible] MDD you also have agitation and the pricing there that the different just wondering how you are approaching this and how you are I guess due discussion with payers might be willing. Thanks.

[Herriot Tabuteau, Chief Executive Officer]

Great. Thanks for the question. With regard 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 very beginning of the second quarter and that's the reason behind you just need there in guidance and Lori. Thank you.

[Lori Englebert]

Hi that’s an interesting question. Regarding pricing so whenever you put pricing discussions with payers typically companies focus on fair and timely access, how large portion of that will be associated with price but the balance of that is we need the price for the value that product brings and so we are working through that right now to make sure that we understand how we appropriately price to represent what value we are bringing to the market.

[Unidentified Analyst]

[indiscernible] agitation.

[Lori Englebert]

Yes, that encompasses the [indiscernible] agitation at all.

[Unidentified Analyst]

Okay. Thanks.

[Operator]

And your next question will come from Matt Kaplan from Ladenburg Thalmann. Your line is open.

[Matt Kaplan, Ladenburg Thalmann]

Hi, good morning and everyone else. I want to congratulate you on the progress during the quarter. Can you give us a sense now that you have submitted the AXS-07 NDA I guess given the [indiscernible] you have in MDD. What are your expectations for potential priority?

[Herriot Tabuteau, Chief Executive Officer]

So as you mentioned we do have great concern for the product and we do believe that we qualify for priority review which is 6 month review. However, that is the determination which is made by the FDA. And the way that it works is that priority review is not automatic and at the time of the NDA filing you do request priority review and is a determination which is made and communicated to the company upon the FDA decision whether or not to file the application. So our plans with regards to launch, etc. are predicated soon a six month review but again that is really up to the FDA.

[Matt Kaplan, Ladenburg Thalmann]

Okay. Helpful and then in terms of ASX-07 I guess we focused a bit on the commercial profit on 05 already. But I guess maybe more for a where are you in the preparation in terms of research again at interaction for 07 given I guess it's kind of the near term NDA filing there

[Lori Englebert]

Yes. Thanks Matt for question. Regarding 07 as I mentioned earlier we have always anticipated that 07 would follow very close to the high end of 05 in terms of launch and therefore we have 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 negotiation exactly we have performed market research but have not started 07 payer discussion just yet.

[Matt Kaplan, Ladenburg Thalmann]

Okay. Great and then last question in terms of Herriot you mentioned you are on track to start the phase 2 for AXS-12 in narcolepsy [indiscernible] next quarter. Can you give us a sense of what you are thinking is in terms of the design of that trial and kind of timeline to completion potential?

[Herriot Tabuteau, Chief Executive Officer]

So with regard to the trial design it will be a parallel design. So it will similar in some ways to the phase 2 trial which we conducted expect the phase 2 trial was cross over design. This will be parallel design. So we expect, we would expect to randomize subjects to ASX-12 and into placebo. And then with regards to expectations around how long it will take to enroll study once we start the study we will 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 we can point to you metrics around the phase 2 enrollment as a reminder that it was 21 patient study which was conducted at roughly 12 sites and that enrolled in approximately six months.

[Matt Kaplan, Ladenburg Thalmann]

All right. Thanks for the added detail.

[Operator]

Your next question will come from Vikram Purohit from Morgan Stanley. Your line is open.

[Vikram Purohit, Morgan Stanley]

Great. Thanks for taking my question. Just had one on AXS-05 for smoking cessation. So I have seen your release but you have an FDA meeting scheduled here for the third quarter. I just wanted to see where you are looking to learn from the meeting with the FDA here and what you think and eventual subsequent pivotal study this indication would look like?

[Herriot Tabuteau, Chief Executive Officer]

So thanks for your question. We are very excited about smoking cessation and on the back of the positive phase 2 data from the small study we are looking to meeting with the FDA to figure out what an efficacy trial would look like. So phase 2 study did look at smoking behavior but that is not a registration end point. Certainly it was very helpful for signal detection which we saw and what we are going to be looking to get out of that meeting is guidance agreement on the design of the next study which would be in efficacy trial. So we are very much looking forward to those discussions. Registration trials in smoking cessation typically the end point is [asthmas] so that is one we would expect for the next study.

[Vikram Purohit, Morgan Stanley]

Okay. Thank you.

[Operator]

And your next question will come from Chris Howerton from Jefferies. Your line is open.

[Chris Howerton, Jefferies]

Hi, good morning. Appreciate you taken the time for questions, congratulation. So I guess [indiscernible] been asking at this point but I guess for 05 with respect to Alzheimer’s disease agitation, there is a possibility and we are going to get increased competition within that space over the next couple of years with a variety of companies developing therapeutic space I guess how the [indiscernible] competing in this landscape particularly obviously as we all know safety is the key concern for this patient population. Thank you.

[Herriot Tabuteau, Chief Executive Officer]

Thanks for a question. It's a very interesting and serious disease area. The term unmet medical need gets thrown around quite a bit but here this would be a good [indiscernible] yes it'd be yes so you're talking about a disease where there currently is no product that is approved and then the drugs that they're used off label have bought black box warnings 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 improved 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. 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 just 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 theoretical when we have not seen positive data from other companies.

[Chris Howerton, Jefferies]

Okay. Alright. Well, thank you Herriot. Appreciate it and I also look forward to that as well. Thanks.

[Herriot Tabuteau, Chief Executive Officer]

Thank you.

[Operator]

And your next question will come from Yatin Suneja from Guggenheim. Your line is open.

[Unidentified Analyst]

Hey guys this is Eddie on for Yatin. Thanks for taking my question. So just to follow up on TRD, can you, given what you saw on 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 timelines to get to an SNDA and TND and how will the MERIT data come in later this year sort of influenced that path? Thanks so much.

[Herriot Tabuteau, Chief Executive Officer]

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 where we do not intend to conduct another phase 3 trial in treatment resistant depressions what we have done 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 to prior treatments.

So from that perspective we're very happy that the STRIDE study was conducted, we think that 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 as is in a scientific setting.

[Unidentified Analyst]

Great. Thank you so much.

[Operator]

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 Raghuram Selvaraju from H.C. Wainwright. Your line is open.

[Raghuram Selvaraju, H.C. Wainwright]

Thank you so much for taking my questions 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 a triple or even a potential quadruple threat in the CNS neuropsych space and in particular if you could talk through, how you anticipate the different sales and marketing strategies to be taken with the 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?

[Herriot Tabuteau, Chief Executive Officer]

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

[Lori Englebert]

Yes. Hey Rag thanks for the question. It's a little bit difficult question to answer at this point in time. Adjutation we need to see how the trial finalizes but we are absolutely always thinking about how we leverage the salesforce, when we leverage the salesforce and what that overlap of position might look like. Again as we built our salesforce sizing and design and structure we did that with the understanding that we would have follow-on indications coming in particularly different disease areas and also different treating physicians. So we've taken great efforts to ensure there's efficiency there, if that were to happen.

[Raghuram Selvaraju, H.C. Wainwright]

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 feel a totally separate salesforce in order to potentially market AXS-05 in that indication as well?

[Herriot Tabuteau, Chief Executive Officer]

Yes Rag 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 but those would be great questions and great problems to have which would certainly solve should we have positive data.

[Raghuram Selvaraju, H.C. Wainwright]

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 filiable approvable application in fibromyalgia?

[Herriot Tabuteau, Chief Executive Officer]

We have 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 view to be unique data in this area which is still an area of high unmet medical needs. As a reminder there are only three approved products to treat fibromyalgia. It is the condition that has a variety of symptoms, many of which are not addressed by the small number of currently available treatments.

[Raghuram Selvaraju, H.C. Wainwright]

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.

[Nick Pizzie, Chief Financial Officer]

Hey Rag, this is 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 [indiscernible] calculation when we do that, so and it is amortized over a four years period typically for our stock based comp. So it wouldn't be all in one year when we have an impact from the field force.

[Raghuram Selvaraju, H.C. Wainwright]

Thank you.

[Operator]

And your next question will come from Ashwani Verma from Bank of America. Your line is open.

[Ashwani Verma, Bank of America]

Hi there. Thanks for taking the question. I just had one, so in terms of the AXS-05 pattern 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 put into the specific attributes of the drug for the MDD label in the situation. Just curious how many of the patents would meet that criteria?

[Herriot Tabuteau, Chief Executive Officer]

Hi Ashwani thanks for the question. 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 or orange book listable and the other point to mention is that most of those patents provided protection out to 2034, the more recent ones provide protection out to 2040. And in addition the new patents encompass different families of patents. So not only do we have pharmacogenetic patents but we also have a method of treating disease patents. Furthermore we would expect that the families would continue to expand.

[Ashwani Verma, Bank of America]

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

[Herriot Tabuteau, Chief Executive Officer]

So I'm not certain of which formulation patent you're referring to? Are you referring to a particular patent? Typically what would we do 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 the method of treating a disease and I think what I was referring to is additional patent families which we would expect to defile in the future so to further expand the patent portfolio.

[Ashwani Verma, Bank of America]

Got it. Thank you so much.

[Herriot Tabuteau, Chief Executive Officer]

Yes. Thank you.

[Operator]

Your next question will come from David [indiscernible] your line is open.

[Unidentified Analyst]

Hey thanks for taking the questions and fitting me in here. So just a quick couple. You talked about the Digital Centric approach to the salesforce and the launch and I'm just curious as to what gives you confidence that type of approach detailing positions in that way would be successful versus a more traditional in-person effort by the salesforce?

[Lori Englebert]

Hey David thanks for the questions. Yes, we have high confidence mostly based on data. We do know that the psychiatrists and neurologists are two 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 is actually higher than data even six 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 we're going to use data analytics to make sure that we're approaching them correctly.

[Unidentified Analyst]

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

[Herriot Tabuteau, Chief Executive Officer]

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 dwelling patients is one, you want to prevent patients from actually being institutionalized. So if you can't 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 there's no reason to think that the pharmacology is going to change depending on the setting.

[Unidentified Analyst]

Got it. Great. Thanks so much for taking my questions.

[Herriot Tabuteau, Chief Executive Officer]

Thanks David.

[Operator]

We have no further questions. Thank you. I turned the call back over to the presenters for closing remarks.

[Herriot Tabuteau, Chief Executive Officer]

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.

[Operator]

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