Good morning, ladies and gentlemen, and welcome to 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..

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 ended December 31, 2019 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 and the source of future clinical trials, regulatory plans, future research and development 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 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 weight on these forward-looking statements and the company disclaims any obligation to update such statements. Joining me on the call today are Dr.

Herriot Tabuteau, Chief Executive Officer; Dr. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs; Dave Marek, Chief Commercial Officer; and Nick Pizzie, Chief Financial Officer.

Herriot will first provide a review of significant corporate and clinical developments for Axsome over the course of the past year, and describe upcoming milestones. Following that 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 fourth quarter and full year 2019 results conference call. 2019 was a transformative year for Axsome as we generated important clinical data for all of our investigational medicines, which we're developing for serious and difficult to treat CNS disorders.

The many important achievements of 2019 included positive NDA enabling clinical trial readouts for AXS-05 in depression, and for AXS-07 in migraine, propelling Axsome potentially towards commercial stage as early as next year. In addition, our AXS-12 product candidate for narcolepsy is progressing to Phase 3 based on positive Phase 2 results.

And throughout collaboration with Pfizer, early this year, we expanded our Phase 3 pipeline with the addition of AXS-14 for the treatment of fibromyalgia. All in all, we now have four differentiated CNS product candidates in clinical development.

All of which have demonstrated efficacy in controlled trials, two of which are pre NDA, with the other two entering or having completed Phase 3 trials. These product candidates provide new mechanisms of action and potentially faster, greater and broader efficacy is compared to currently available treatments.

Our investigational medicines therefore have the potential to change the current standard of care for difficult to treat brain disorders and transform the lives of patients living with these conditions. We expect 2020 to be a year of continued operational, clinical and regulatory progress.

Preparations are underway for our planned NDA filing of AXS-05 in the treatment of major depressive disorder or MDD. AXS-05 has the potential to be the first and only oral NMDA receptor antagonist with multimodal activity for the treatment of depression.

In December, we announced positive results from a Phase 3 GEMINI trial of AXS-05 in patients with confirmed moderate to severe MDD. In this study AXS-07 met the primary endpoint by rapidly, substantially and statistically significantly improving symptoms of depression as compared to placebo.

The positive results from the GEMINI trial along with the previously completed MOMENTUM trial of AXS-05 in MDD support an NDA filing for AXS-05 in the treatment of MDD. And we are on track to file this NDA in the fourth quarter of 2020. AXS-05 has been granted breakthrough therapy designation for the treatment of MDD.

Preparations are also underway for our planned NDA filing of AXS-07 in the acute treatment of migraine. AXS-07's multi mechanistic approach is designed to provide enhanced efficacy as compared to currently available treatments.

In December, we announced the positive results from a Phase 3 momentum trial of AXS-07 in migraine patients with a history of inadequate response to prior acute treatments.

In this study AXS-07 met the co-primary and key secondary endpoints by significantly relieving migraine pain as compared to placebo, and as compared to the active competitor rizatriptan.

The positive results from the MOMENTUM trial support an NDA filing for AXS-07 in the acute treatment of migraine and we remain on track to file this NDA in the second half of 2020. With these two planned NDA filings Axsome is on track to transition to commercial stage potentially as early as next year.

And to that end, we have been building out our commercial capabilities. In December we also announced positive top line results from the Phase 2 INTERCEPT trial of AXS-12 in the treatment of narcolepsy.

In this study, AXS-12 significantly reduced cataplexy attacks and excessive daytime sleepiness and improved cognitive function, sleep quality and sleep related symptoms. These results point to a differentiated clinical profile for AXS-12 with the potential to address all the key symptoms of narcolepsy.

Based on these positive results, AXS-12 is scheduled to enter Phase 3 clinical trials in narcolepsy in the second half of this year. We expect the development of AXS-12 to accelerate as a result of our agreement with Pfizer, which we announced in January. This agreement covers an exclusive U.S.

license to Pfizer's clinical and nonclinical data, intellectual property for reboxetine, an active pharmaceutical ingredient in AXS-12. This agreement also expands our late stage CNS pipeline by providing us exclusive rights to develop and commercialize a new product candidate esreboxetine or AXS-14 in the U.S. for the treatment of fibromyalgia.

AXS-14 has previously demonstrated positive and statistically significant results in Phase 3 and in a Phase 2 trial in the treatment of fibromyalgia. In addition to its effects on pain and function, AXS-14 demonstrated in both of these studies, an effect on fatigue, but difficult to treat symptom of this condition.

Excellent plans to meet with the FDA this year to discuss the further clinical development of AXS-14 for fibromyalgia. Turning now to our ongoing efficacy trials. We recently completed randomization into our STRIDE-1 trial of AXS-05 in treatment resistant depression and into our INTERCEPT trial the AXS-07 in the early treatment of migraine.

We remain on track for top-line results from both of these trials before the end of this month. Our ADVANCE-1 Phase 2/3 three trial of AXS-05 in the treatment of agitation associated with Alzheimer's disease is now more than 80% enrolled. And based on this trend, we expect top-line results from this trial in the third quarter.

In summary, over the balance of the year, we look forward to several important milestones. Including the NDA filings for AXS-05 in MDD, and AXS-07 in migraine anticipated in the fourth quarter. Top-line results from the STRIDE-1 trial of AXS-05 in TRD and the INTERCEPT trial with the AXS-07 in migraine this quarter.

Top-line results from the ADVANCE-1 trial of the AXS-05 in Alzheimer's disease agitation in the third quarter. And initiation of Phase 3 trials of AXS-12 in narcolepsy in the second half of this year. I would also like to recognize and congratulate Mark Jacobson on his recent appointment as Chief Operating Officer.

Mark has been a valued member of the Axsome team since 2014. And served as Senior Vice President of Operations since 2017. I will now turn the call over to Nick to provide financial update for full year of 2019..

Thank you, Herriot and good morning, everyone. I will focus on key highlights in the quarter and provide some financial guidance. R&D expenses were $19.2 million for the quarter ended December 31, 2019 versus $7.2 million for the comparable period in 2018.

This increase was due to a significant number of new clinical trials that were conducted during the quarter as compared to the prior period, including the CONCERT, GEMINI, MOMENTUM, INTERCEPT trials, along with the AXS-05 and AXS-07 open label safety studies. In addition to the ongoing progress of the STRIDE-1 and ADVANCE-1 trials.

G&A expenses were $5.2 million for the quarter ended December 31, 2019 and $2.3 million for the comparable period in 2018. The change was primarily due to personnel costs, mainly from higher stock compensation expense, along with the build out of the commercial functions.

In December, we completed an underwritten public offering that yielded aggregate gross proceeds before deducting offering expenses of approximately $200 million. SVB Leerink and Morgan Stanley acted as joint book running managers for the offering.

As a result, we ended the fourth quarter with $220 million in cash compared with $44 million at the end of the third quarter. We believe that our current cash position will be sufficient to fund our anticipated operations based on our current operating plan for at least two years. That concludes our fourth quarter 2019 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 the line of Charles Duncan with Cantor Fitzgerald. Please go ahead..

Good morning, Herriot and team. Congratulations on a very good year and last year and what could prove to be a very interesting one this year. I wanted to ask you just a couple of quick questions on the pipeline and then maybe one on commercial build. For AXS-05 relative to the upcoming TRD results.

I guess I’m wondering what you're thinking about the different scenarios that could be and the impact on the regulatory and/or commercial strategy for AXS-05.

Can you lay out a couple of scenarios of either the drug clearly working, the drug may be working or the drugs not working in TRD?.

Thank you, Charles. With regards to TRD, what's nice about that study is that it is targeting a patient population which is in great clinical need. What's nice about our regulatory strategy and our commercial strategy is that we have now demonstrated positive efficacy results in the treatment of MDD with very differentiated product profile.

And we're very much on track to filing our NDA. And our commercial prep is also underway assuming that the product gets approved for MDD. If the TRD trial is positive, or if it's negative or if it's mixed, it will not have any impact on our filing strategy. However, should the study be positive, it would be included in our NDA package.

And we believe that it would be included in the clinical trial section of the package insert. It would not change the indication for the product, the indication would still be MDD. In order to get a formal label for treatment resistant depression, we -- it is our understanding that the FDA would require a second trial in TRD.

Importantly, as we said before, that study could be a placebo control trial. So, under the vary scenarios, assuming that the study is positive or if it's negative, or if it's somewhere in the middle, I think we're very well positioned. We will not speculate on what the results could be. But we certainly have scenarios planned internally.

And we're very much looking forward to the readout before the end of the month. Yeah. And just from a commercial perspective, I'll turn it over to Dave. .

Good morning, Charles, thank you for the question. As we think about the commercial build out relative to TRD. As we've talked to physicians, the good news is that with MDD, we have the broader indication that already gives us access to a broad range of patients with MDD.

And when we talk to physicians, given the clinical data that we've already produced, there's quite a high degree of enthusiasm towards AXS-05 already. So the question is, well, if we have positive results with TRD, how does that change.

And I think the single greatest factor that we've seen in terms of talking with clinicians, is it increases their enthusiasm for the patients that they would view for appropriate for AXS-05. So if you look at that there's already a tremendous degree of enthusiasm for MDD, in general.

And this would even further strengthen their conviction around either more patients or perhaps deepening the range of patients that they would consider appropriate for AXS-05..

Yeah, that's helpful. That's actually consistent with our KOL diligence as well. So it doesn't seem like TRD is needed. It's a nice to have. Moving on just quickly to 07. I think Herriot you mentioned 2H '20 for an NDA filing. And I read in the press release said it was 4Q.

So is that just a slip or is it possible that the NDA filing for AXS-07 could actually come yet in the third quarter?.

It is possible that it's coming in the third quarter. Our formal guidance is the fourth quarter though. And the gating factor to the NDA filing is our safety database, which needs to include 100 patients treated for one year, and that we do have an open label safety extension trial ongoing.

And so we will need to anniversary that 100 patients at the one year point in order to file the NDA..

Okay, final question commercial capabilities. You say have them being built, I guess instead of what you've been doing, maybe what you will do in terms of sizing and timing.

Do you have any thoughts on really the size of the field force that you'll need to mount to effectively market these two drugs? And somewhat different are although somewhat the same markets for prescribers?.

Regarding the commercial build out you're absolutely correct. When we think about building out our commercial team, we have a solid foundation now. And we want to make sure that we're adding the appropriate resources kind of at the appropriate stage as we march towards potential launches coming.

When we think of field force the benefit of clarity around both having MDD and migraine allows us to think in a highly efficient way, as you mentioned around our prescriber base. And we have been looking at a variety of scenarios in terms of field force sizing structure, et cetera.

I think one of the kind of tenants that we've been using is how do we make sure that we have a very efficient launch.

Where we're looking at using data and analytics in a very contemporary way to ensure that we are targeting those prescribers who have the highest willingness to prescribe and also ability to prescribe given what we believe the payer environment could be.

And so you could envision a very efficient and targeted launch with the ability to scale very quickly as prescriber adoption and access open up. We would be ready to scale very quickly. So think of an efficient sales force presence at the beginning and one that can scale very quickly..

It sounds like more on that later on this year or into next year as we get closer with the NDA filings?.

Yeah, correct. I mean, if you think about the field force being hired, about six months in advance. We want to keep our options active as we approach that time period, and make sure that we're looking at the latest data, the latest analytics, and that will help us solidify our final sales force size and structure as we get a little closer to launch..

Sounds good. Thank you for taking my questions..

Thank you..

Your next question comes from the line of from Ram Selvaraju with HC. Please go ahead..

Thanks very much for taking my questions. I was wondering if maybe we could start with the narcolepsy program.

Can you give us a sense of how large the scope of the clinical trial program is going to be in the pivotal setting? If you have a sense of that at this juncture? And whether you expect to seek an SBA from the FDA regarding this? And then also on esreboxetine.

I was wondering whether you have at this point a sense of whether the discussions with the FDA are going to center around the possibility of being able to file with the data that Pfizer has already generated or if they're going to center around the need for additional clinical development work in the pivotal setting, before you're able to potentially submit an application for that product candidate in fibromyalgia?.

Thanks, Ram, for the question. With regards to narcolepsy. We have gotten feedback already from our initial interactions with the FDA with regards to the Phase 3 plan. And before we actually launch that Phase 3 trial actually we're thinking two Phase 3 trials or narcolepsy.

We wanted to refine those plans and make sure that the FDA thinking has not changed. So, stay tuned with regards to that.

What I would say is, if you look at the results of our clinical trial, the results did reflect the pretty large treatment difference even with approximately or the equivalent of 20 patients per arm assuming that this had been a parallel design trial. With regards to what has been sized in previous trials, for registration in cataplexy.

For example those studies in the past have been in the range of around 30 to 40 patients per treatment arm. So, that gives you a sense. And for excessive daytime sleepiness the numbers do go up from there in order to adequately power studies. But, we'll be coming back to you, as we finalize the Phase 3 trial designs before we launch those studies.

With regards to esreboxetine, as I mentioned, we do intend to meet with the FDA to discuss the clinical development plan for esreboxetine going forward. We think this is a very differentiated product candidate, especially with regards to the breadth of symptoms of fibromyalgia as I said that it can treat.

As a reminder, there are only three products that are currently approved to treat fibromyalgia in the US. So, we're looking forward to those discussions.

Obviously, as part of those discussions, we will like to understand the FDAs view of the data that has been generated to date and the appropriateness of those clinical trials potentially for registration. Certainly that'll be an important point of discussion at least as it relates to any further clinical trial that we may have to conduct..

Okay, thanks for that clarity. And then I wanted to ask a question regarding AXS-05 for the ADVANCE-1 target indication.

So, I was hoping you could maybe comment on perspectives regarding what the path forward would be for AXS-05 assuming ADVANCE-1 is positive?.

Assuming ADVANCE-1 generates positive results, the assumption, our working assumption is that we would need one additional trial, one additional efficacy trial in Alzheimer's disease agitation. As a reminder, this is an area of high unmet medical need. There currently is no product that is approved to treat Alzheimer's disease agitation.

We're happy with the progress of the clinical trial thus far. And this is a pivotal trial. And so it would make sense obviously that we would need an extra trial in order to get the product approved. There has also been the feedback from the FDA. So, that that is our working assumption..

Okay, and then just a couple other very quick ones. I remember that at one point, you were talking about the possibility of monetizing some of the intellectual property that Axsome holds in the area of I believe it was complex regional pain syndrome.

Is there any updates on that or any way in which you see that situation evolving in the near-term?.

You are correct that, we do have other assets, which are not core assets. So, our core focus right now is our CNS pipeline which consists of four product candidates in active clinical development. And these other assets, we're pretty excited about. And we think that they are potential sources of non-dilutive funding.

And so those have been placed into a separate business unit. We took in order to facilitate business development negotiations. We currently do not have any immediate update on that business unit. However, as things progress, if there is anything worth updating you on we certainly will. .

Okay, perfect. And then this is just a question for David. I was wondering if at this juncture since a lot of the clinical efficacy data for AXS-05 and indeed also 07 is out there. If you are receiving inbound interest from people who might potentially become part of the sales and marketing team at Axsome.

And if you could perhaps comment just qualitatively on the caliber of these people, potentially some of their background in promoting drugs in the CNS and neuropsychiatric spaces? And to what extent this potentially gives you confidence that you can establish a sales and marketing team that would be best of breed as it were in the industry, as and when 05 and 07 are approved?.

Well, thank you, Ram. I think you're exactly right that as more and more information comes out, not only regarding those programs, but the company itself. And there are a couple things that I think gets people really excited.

If you have been in the depression space or the migraine space and you're watching what's happening in terms of the evolution of new potential therapies. There are a lot of commercial people out there who are just as excited as our prescribers are around the potential of what we can do in the marketplace and how we can serve patients.

Also, I think there are commercial individuals who are very excited about the idea of a highly efficient and contemporary launch. And so we kind of disproportionately attract those types of talents, whether that's within the marketing function or the data and analytics function.

So we feel very good about the type of interest that we're receiving, unsolicited, but also through contacts and relationships that we have in the industry. We feel very, very confident that we're going to be able to feel to very strong sales force as well as other commercial talent..

Great, thank you very much..

Thank you. .

Your next question comes from the line of Yatin Suneja with Guggenheim Partners. Please go ahead..

Hey, guys, thank you for taking my question. And Mark congrats on the new role. Just a couple questions on a few things. Maybe we'll start with TRD Plus.

Can you talk a little bit about how you are qualifying and non-responder in the STRIDE study? And then in terms of the dose that you might be using in the open label phase and the randomized phase, is there a reason to believe that you might be using a different dose in the open label what should be randomized phase? And then I have two follow ups. .

Thanks, Yatin for the question. And I'll turn it over to Cedric to answer that..

Yeah, thanks. So first of all, with regard to treatment resistant depression and the -- I think it was the definition of treatment resistant depression that you'd asked about --.

In non-responder. .

Non responder, right. So, there's a standard approach that just as a reminder within the open label period, the patient is being treated with the bupropion. And if they fail to respond, they're randomized.

Now with regards to both the dosing and the criteria by which we measure response or non-response to start, do we disclose that once we have top-line data, which will be before just before the end of the month. So we're on track for that. .

Okay. Understand, and then in terms of the -- again on the dose, like have you manufactured your own dose to use in this study for bupropion or are you using a commercially available? Because I remember in the ASCEND study, the dose that you have used is not commercially available, so you had to make your own dose.

So help us understand the situation here. And then move to the agitation side can you maybe comment on what was the reason for delay? And why it got pushed from first up to Q3? Thank you..

So, yes, thanks for the additional questions. With regards to drug product which is used in clinical trials, as a reminder, clinical trials do require that products be blinded. And so therefore with the drug product for the various arms and in the various treatment periods have to be made that they match in appearance.

With regards to Alzheimer's disease, agitation, and our updated guidance. So, our previous guidance was the first half of this year and we have talked about roughly mid-year. That has not changed significantly. What we wanted to do was to build in some potential buffer as you know there are some external factors.

And not to talk too much about the impact of the corona virus, but it is something that that we do have to be mindful of given that Alzheimer's disease agitation is targeting a patient population, which is elderly. Right now, we've not seen any impact.

But we do think that it is prudent to in our range of guidance, make sure that we take into account any potential eventualities..

Got it. And thank you I'll get back into the queue..

Your next question comes from line of Marc Goodman with SVB. Please go ahead. .

Yes, morning, Dave. I was wondering if you could talk about the migraine space a little bit. Obviously, a crowded market with, some new players coming in one that's already launched and doing pretty well.

Talk about how you view the market, how that's changed and how you're thinking about differentiating your product when it comes out?.

It will get more and more. Thank you. Well, I think when we look at the migraine market, for those of us who've been associated with a migraine market for many years, it couldn't be a more exciting time. And that's really good for clinicians. And it's good for patients.

So certainly we have long wanted to have more options to provide for patients and really help them better manage migraine. When you look at the frustration in the marketplace, the first place we go to and I say this often is to really clarify what are we solving for in terms of the frustration or the unmet need in the marketplace.

When we talk to clinicians and patients consistently in the acute therapy setting, what physicians and patients are frustrated by is just pure efficacy. While there are a variety of needs out there, the one that rises to the top and in our research, it was 8 out of 10 physicians prioritize improved efficacy was their greatest unmet need.

And so we built a clinical program around solving that issue of how can we improve efficacy. And I'm really proud of the clinical program we put together because I think with MOMENTUM, it really focused on answering the question that a clinician faces every single day.

So, you start with who's the right patient population with the greatest unmet need, and those are those who have failed, at least one prior therapy. And those are the types of patients that we enrolled in MOMENTUM. Those that were treatment experienced and had a prior sub optimal response to their acute therapy.

And again, those are the patients that physicians tell us that they are dealing with day-in and day-out. And then we took the next step and said, okay, well, what are their treatment options and what would they be faced with.

And in MOMENTUM, we went head-to-head against rizatriptan, which is largely viewed as one of the most effective treatment options out there, certainly one of most effective triptan. And by showing superiority, we think that we've really helped clinicians understand for their most difficult patients, where we have the next best step.

And those are the data that we think will be highly differentiating in the marketplace. The right patient that they're dealing with, with the right clinical data that allows them to make a treatment decision that we think can deliver better efficacy, which is what the marketplace is looking for.

And I think that's really the core of our differentiation and why we think there is tremendous enthusiasm for AXS-07.

And you may recall in our mindset survey we asked migraine treating physicians, their degree of enthusiasm towards AXS-07, should we be superior to rizatriptan? And I think, we've talked about those results where the vast majority of physicians say they would prescribe AXS-07 over currently available treatments, but also over the emerging treatments as well.

So we see a very strong commercial opportunity to benefit patients with AXS-07..

And how does the INTERCEPT study play into it?.

Well, I think what INTERCEPT does is it helps inform and provides a greater foundation for how they treat and direct patients in the real world setting. We know in the typical clinical trials we need patients to wait until their pain is moderate to severe. And those data are very helpful for registration processes and et cetera.

When we look at how clinicians typically tell their patients to administer their acute therapy, they say take it at the first sign of migraine pain. And so we think that INTERCEPT will provide kind of the real world setting information for how we think this product will perform in a manner that they'll likely instruct patients to administer.

So we think it is additional information that's not required for the NDA filing, but will be important in the setting as we educate physicians around the utility of AXS-07..

And last question, as you're thinking about the sales force, is it going to be one sales force that sells both products, the progression product and this one? Will it be two separate ones? How much overlap is there?.

Well, as mentioned earlier, we will still look at options around -- looking at both migraine and depression and how we -- the size and structure of that field force. So while we have a variety of options, we haven't landed, specifically we'll do more work around that.

I will say though, we will look for efficiencies across promoting both migraine and depression. There is some overlap and mainly in the primary care setting, as you can imagine, with some physicians, who are high prescribers of both. And we would certainly take advantage of that synergy.

The degree to which we're still evaluating as we look at our options. So we haven't landed on one field force or two, but what we will do as we make that decision and look for the greatest efficiencies that we can glean..

Thanks..

Your next question comes from the line of Matt Kaplan with Ladenburg. Please go ahead..

Hi, good morning, guys. Congrats on the progress. Just wanted to zero in a little bit more on STRIDE-1 given the near-term readout of results expect there. So can you please remind us of the sizing and the powering of the study? I guess, given the fact that you have continued enrollment to build your safety database.

Can you give us a sense of that?.

Good morning, Matt and thanks for the question. So in terms of sizing, the last update that we gave was that the study had randomized approximately 300 patients. That was at the end of November. And so the final number will be north of 300.

In terms of the powering of the trial, the study was powered at the 90% level to detect an effect size of somewhere between 0.3 and 0.35, which is in line with the effect sizes of antidepressants that have been shown to work and they have been currently approved..

Great. Thank you. And then in terms of the open label extension study for 05 that's enrolling both MDD and TRD patients.

How is that progressing and can you give us an update in terms of how many patients you expect ultimately in the open label extension?.

That study is progressing well. As you know, that is a gating factor to us filing an NDA. We do need to build a safety database of 300 patients treated for 6 months and 100 patients treated for one year. And we're on track to do that. So we're pretty happy with the way that that is currently enrolling.

It is enrolling in a pace that will allow us to meet our guidance of filing an NDA before the end of the year..

Okay, thank you. And I guess just going back to -- following up on some questions that we had on AXS-14 esreboxetine for fibromyalgia.

Can you give us a sense in terms of the potential regulatory paths forward for esreboxetine and fibromyalgia?.

Yes. So, we first want to meet with the FDA. As a reminder though, esreboxetine has completed two efficacy trials of significant size. One was a Phase 3 trial which enrolled and randomized over 1000 patients. And that study was positive. And there was also a Phase 2 trial which was all the positive.

Both of these studies were randomized, double blind, placebo controlled trials. And so we certainly will want to get the FDAs feedback on those clinical studies. Those studies were run by Pfizer. So we want to make sure that we get feedback from the FDA in terms of what else would be required in order to file an NDA.

We will not speculate on what those requirements could be and until we until we meet with the agency..

Great. Very helpful. Thank you and good luck going forward. .

Your next question comes from line of Bert Hazlett with BTIG. Please go ahead..

Thank you. I just have a couple of quick ones. Just with -- you have a lot on your plate with a number of different indications. Where does that AXS-05 the smoking cessation indication set in terms of urgency, and in terms of corporate priorities? Thanks..

Thanks for the question. So you are correct that AXS-05 does have a number of potential indications, and we do have a lot on our plate. It was one of the challenges that we're facing, and that we're keeping in mind is the need to focus while at the same time avail ourselves of the various opportunities in the pipeline.

So, our priorities clearly this year are to make sure that, we file our NDAs in a timely manner and also that those filings are of significant quality. So, that is our top priority which is our NDA filings. And then beyond that is advancing our product candidate in narcolepsy into Phase 3, based upon the very positive Phase 2 data.

So, I'd say that's priority number two. And then of course, getting the feedback on AXS-14, given a very positive efficacy results there.

And then we absolutely will be meeting with the FDA this year with regards to smoking cessation to delineate a path forward there and understand what the clinical development, what the further clinical development for that indication will look like..

Okay, thank you.

Could you just remind us of the CNS [ph] progress or characteristics or status of 05 at this point?.

So, the clinical trial material for AXS-05 for our AXS-05 trials have been made at commercial scale. So, we're in very good shape there and they've also been made at the -- they've also been made at the contract manufacturer that will be manufacturing the commercial supply.

There are registration batches which must be made specifically for the purpose of submitting an NDA. And so that work is underway. .

Thank you and then just one on migraine.

Does it make sense to have a study in combination with a long acting CGRP [ph] with an acute migraine therapeutics such as you have with 07? Does that make any sense commercially at all?.

We certainly don't see any reason why ASX-07 could not be administered with other types of therapies. Right now we're focusing on getting the product approved. And it will be interesting to see how clinicians eventually choose to use it as part of their armamentarium..

Okay, thanks. That's all for me. Thank you very much..

Your, next question comes from line of Myles Minter with William Blair. Please go ahead..

Hi, guys. Thanks for taking the questions and congrats Mark on the new position at the company. Just the first question is on ADVANCE. 80% enrolled, push the gotten slightly out to third quarter.

I'm wondering whether you're proactively, cautioning your physicians to enroll new patients into that trial currently given, the unfortunate risk with [indiscernible] at the moment in that highly susceptible population. And also you mentioned 80% enrollment.

I'm wondering what proportion of patients were enrolled in that trial at the December 2018 timeline, where you discontinued enrollment into the bupropion alone arm. .

So, thanks for the questions, Myles. The -- with regards to cautioning physicians around enrollment into the trial. I mean, we're not currently doing that. But what we are doing is monitoring very closely from the clinical trial sites, any information that they have or any concerns that they might have with regards to enrollment.

Currently, we're not hearing anything that is of concern, but it is the situation that we're monitoring pretty closely. And with regards to the percentage of patients at the time of the interim analysis. The interim analysis as a reminder was conducted at the 30% enrollment point.

So that should allow you to get a sense of what the subsequent enrollment was after that it was enrolled. So 30% enrollment point and remember the size of the trial was 435 subjects total. .

That's helpful. Thanks for that. And then maybe a question for, Dave. To some diligence we've been doing suggests that relation specialty centers, they're sort of using SSRIs and rather than waiting for six to eight weeks for a response there. They’re trying to say an early response in two weeks with those drugs, maybe a 20% improvement.

To predict whether those patients are truly going to have a response down the track? Just looking at the data from GEMINI and ASCEND and the early rapidity of response. I'm wondering in your conversations with clinicians, both in specialty centers and in PCPs. Whether a focus on their behalf is actually on the rapidity of effects.

And maybe not so much focused on mattress [ph] but maybe on some of those patients quality of life.

Question is, which are more routinely used in the clinic? What are you hearing from the community? What are they most excited about this products case?.

Good morning, Myles. Thank you for the question. We are hearing some of the same in our research around what physicians are looking for. And when we put the current data that we have for 05 in front of specialists, one of the things that they light up about is really around the rapidity of effect.

But also what they get excited about is kind of the reason to believe that.

And when you look at the NMDA plus multimodal activity, they're really hungry for a different pathway that kind of gets them off the merry go round of the SSRIs, SNRIs and they're looking for another pathway, and one that would be potentially delivered in a very patient friendly way. So that gives them reason to really sit up and look at our data.

And then when they see the rapidity of effect and the robust nature of effect that's where they start to look at this as certainly for patients that they've struggled with, who are treatment experience, but also they start to move up very quickly earlier to think about patients where they would want that rapidity of effect and moving it up earlier as foundational therapy.

So we're very excited about the response we're getting from the clinical profile. We think the more there is focus on rapidity of effect is good for clinicians, and it's very good for patients. And we think that we're going to be able to fit nicely in that unmet need..

So just a follow up. Does that logic change between specialist centers that are most likely monitoring their patients consistently over that early treatment period versus a PCP that Marc just described. And then come back six weeks later, and not actually monitor that patient's response early on..

Yeah, I mean, I don't have the data to answer that question.

But intuitively, I think it makes sense that those centers who are very actively monitoring rapidity of effect and the types of patients that they may be seeing could be very different in terms of sense of urgency that we might see that we might see with primary care specialists out in the field.

I think the desire is the same that everybody wants their patients to get better sooner. But I think the adoption curve could be different across those two areas of treatment..

Fair enough. Thanks for the questions and congrats on the year. .

Thank you, Myles..

There are no further questions at this time. I will turn the call back over to the presenters for closing remarks..

Well, thank you all for joining us on the call today. Axsome is committed to accelerating the invention, development and adoption of life changing medicines for many people facing on satisfactory treatments for CNS diseases. We anticipate a number of important milestones over the balance of the year and we look forward to updating you on our progress.

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This concludes today's conference call. You may now disconnect..