Good morning, ladies and gentlemen, and welcome to Axsome Therapeutics Third Quarter 2019 Financial Results Conference Call. Currently, all participants are in a listen-only mode. Later, there will be a question and answer session, 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, Senior Vice President of Operations 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 third quarter of 2019 crossed the wire a short time ago and is available on our website at www. 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 funding 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 who will begin the call by highlighting our recent achievements and upcoming clinical milestones; Dr. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs; Dave Marek, our Chief Commercial Officer; Nick Pizzie, Chief Financial Officer who will provide a financial update.

I would now like to hand the call over to Herriot..

Thank you, Mark. Good morning, everyone and thank you all for joining us on the call today. So far, 2019 has been very productive for Axsome.

We've significantly advanced our three clinical stage CNS product candidates, which are being evaluated in six efficacy trials, including five Phase 3 trials and one Phase 2 trial across five different indications.

It is a highly active time for Axsome and a potentially important time for patients and clinicians as these studies are fast approaching completion with top line results expected by year-end for several of these clinical trials.

If successfully developed, our first-in-class or best in class investigational medicines have the potential to transform the lives of many of the millions of patients who are currently failed by existing treatments for their CNS disorders.

Before I provide an update on our programs and upcoming clinical milestones, I would like to introduce you to our Chief Commercial Officer, Dave Marek, who joined the Axsome team in August. Dave joins us from Amgen, where he was Vice President and General Manager of the Neuroscience Business Unit.

Prior to Amgen, he held Executive positions at WebMD and at Saatchi & Saatchi healthcare advertising. Earlier in his career, he maintained commercial roles in CNS therapeutic areas at both Eli Lilly and Company and AstraZeneca. I would like to turn it over to Dave.

Dave?.

Thank you, Herriot. Let me say how excited I am to join the Axsome team and lead the commercial efforts to ensure our novel investigational medicines, bring the therapeutic advantage needed for many of the millions of people affected by CNS disorders.

It's an exciting time to have such a important data unveiled in the coming weeks and possibly lead to two NDA filings next year. The Axsome leadership team has been focused on thinking differently and efficiently in accelerating our clinical programs.

And I'll ensure our commercial efforts follow the same philosophy of effectiveness, efficiency and maintaining our patient focus at the center of everything we do.

As a commercial leader, it will be my responsibility to ensure the attractive clinical profile of our products is matched with proper physician education as well as fair and timely payer access to ensure patients who need better treatment options can actually benefit from our therapies.

Herriot?.

Thank you, Dave. I will now provide an update on our programs and upcoming clinical milestones. Beginning with AXS-05, our novel oral investigational NMDA receptor antagonist with multimodal activity. AXS-05 is being evaluated in two Phase 3 depression studies.

The GEMINI placebo-controlled trial of AXS-05 in major depressive disorder or MDD and STRIDE-1 active-controlled trial of AXS-05 in treatment resistant depression or TRD. We completed patient enrollment in the GEMINI study and are on track to report top line results from this trial before year-end.

Patient screening in the STRIDE-1 Phase 3 active-controlled trial of AXS-05 in TRD will conclude by the end of November. This approach allows for meaningful proportion of patients with TRD to be included in the long-term safety database, helping to assure a robust NDA filing.

Based on this timing, top line results from this trial are now expected in the first quarter of 2020 versus previous guidance of the fourth quarter of 2019. Importantly, the anticipated timing of our NDA filing for AXS-05 remains unchanged. We are looking forward to the readout for the GEMINI and STRIDE-1 trials.

Based on the results of the FDA breakthrough therapy meeting for AXS-05 held earlier this year, positive results from either GEMINI or STRIDE-1 would be sufficient along with the previously completed ASCEND trial of AXS-05 in MDD to support an NDA filing for AXS-05 for the treatment of MDD.

Pending the readouts of these studies and NDA filing for AXS-05 is targeted for the second half of 2020. AXS-05 is also being evaluated for the treatment of agitation associated with Alzheimer's disease in our ongoing ADVANCE Phase 2/3 trial.

The ADVANCE trial is approximately 70% enrolled and top line data from this trial is anticipated in the first half of 2020. Turning now to AXS-07, our novel oral investigational medicine with distinct dual mechanisms of action for the acute treatment of migraine.

Axsome has completed enrollment in the momentum Phase 3 trial of AXS-07 in the acute treatment of migraine in patients with a history of inadequate response to prior acute treatments. MOMENTUM is being conducted pursuant to an FDA special protocol assessment and incorporates the potent active comparator rizatriptan.

We remain on track to report top line results for MOMENTUM before year-end. Based on FDA feedback, this trial, if positive, will be the only efficacy trial required to support an NDA filing for AXS-07 for the acute treatment of migraine which is targeted for the second half of 2020.

Last month we initiated the INTERCEPT trial, a Phase 3 placebo-controlled trial in which patients are to administer AXS-07 at the early sign of migraine pain. INTERCEPT is designed to enhance the market readiness of AXS-07 by generating additional information on its potential real-world use.

As the vast majority of specialists believe it is very important for patients to administer their acute treatment at the early sign of migraine pain. Top line results from INTERCEPT are anticipated in the first quarter of 2020. Turning now to AXS-12, our novel, oral, potent, and highly selective norepinephrine reuptake inhibitor for narcolepsy.

We have completed enrollment in the Phase 2 concert trial, which is a randomized, multicenter, double-blind, placebo-controlled trial evaluating the effect of AXS-12 in patients with narcolepsy. We remain on track to report top line results from this trial before year-end.

In summary, between now and the end of the year, we expect top line results from the Phase 3 GEMINI trial of AXS-05 in MDD, the Phase 3 MOMENTUM trial of AXS-07 in the acute treatment of migraine, and the Phase 2 CONCERT trial of AXS-12 in the treatment of narcolepsy.

We anticipate a continuation of significant milestone into next year with top line results from the Phase 3 STRIDE-1 trial of AXS-05 in TRD and the Phase 3 INTERCEPT trial of AXS-07 in migraine, both expected in the first quarter of 2020.

We also anticipate top line results from the Phase 2/3 trial of AXS-05 in Alzheimer's disease agitation in the first half of 2020, and potentially two NDA filings for AXS-05 in MDD and for AXS-07 in migraine in the second half of 2020. Now, I would like to turn the call over to Nick for a financial update..

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 $15.8 million for the quarter ended September 30, 2019 versus $6 million for the comparable period in 2018.

The increase was primarily due to trials that were initiated in 2019 and fully enrolled in the year, which include the GEMINI, MOMENTUM and CONCERT trials, along with the initiation of the INTERCEPT trial and AXS-05 and AXS-07 open-label safety studies.

R&D expenses are expected to decrease substantially in subsequent quarters as multiple trials are or are close to being fully enrolled. G&A expenses were $3.1 million for the quarter ended September 30, 2019 and $2.2 million for the comparable period in 2018. The increase was primarily due to higher stock compensation expense and personnel costs.

We ended the third quarter with $43.6 million in cash compared with $53.8 million at the end of the second quarter. We believe that our current cash position fully funds all ongoing clinical trials and will be sufficient to fund our anticipated operations based on our current operating plan into the second quarter of 2021.

As previously disclosed, we did not anticipate any new equity financings prior to the readout from our Phase 3 efficacy trials. That concludes our third quarter 2019 financial review. I will now turn the call back to Mark to lead the Q&A discussion..

Thank you, Nick. And operator, may we have our first question please..

Yes, sir. And your first question comes from the line of Charles Duncan with Cantor Fitzgerald..

Good morning, guys. Thanks for taking our questions and congrats Herriot and team to all the progress this quarter and this year and entrusting years could continue to be so. Herriot, had a quick question though on GEMINI and AXS-05.

I’m wondering if you can provide a sense of as you’re looking at the blinded kind of [indiscernible] of that trial, how does the patient sample look relative to your expectation in terms of characteristics of the patient? And then in terms of the dropout rate that you had assumed?.

Well, thank you, Charles for the question. As a reminder, the -- one of the things that we try to do with the GEMINI trial was we try to design that study to replicate the ASCEND trial as much as possible. I believe that we would achieve that goal.

And in terms of what we've been seeing with regards to the types of patients that we've enrolled thus far in GEMINI versus ASCEND, its early. The study enrolled quite rapidly, but I'll turn it over to Cedric to see if he have a sense of what the patient demographics might look like between the two studies..

Yes. Thank you, Herriot. Hi, Charles..

Good morning..

So as you know we worked very strong, we are very keen to make sure the design of the GEMINI trial was similar to the ASCEND study with some important distinctions. But we wanted to confirm that they had a diagnosis with MDD that their symptomatology was moderate to severe.

And we are pleased to say that the content and the trials of that -- what we’ve seen so far in terms of as you mentioned, discontinuation for example, that has been very similar to the ASCEND trial. So we're happy with the design and content and I think that’s about it..

Okay. And then if I could ask just a follow-up on AXS-05, regarding the advanced trial in Alzheimer's agitation. There was -- I think an unexpected results out of -- arguably a mindshare competitor with a deuterated form, with a drug that contain deuterated form of dextromethorphan.

And I'm just kind of wondering what you think that says about either conducting studies in Alzheimer's agitation patient or even a drug containing dextromethorphan, because that one didn’t meet its endpoint and you would've anticipated that it did.

Is there anything different about deuterating a dextromethorphan that could make an impact?.

So as you pointed out the study with which you are referring to did use deuterated dextromethorphan as part of their product candidate, that was one of the components. And AXS-05 as you know used is non-deuterated dextromethorphan.

That may be an important difference because the whole point of deuterating a compound is to change its pharmacology somehow, either the way that metabolize, or unintentionally maybe the way that it interacts with DNS receptors.

There is preclinical data that has been published, which does indicate that deuterated dextromethorphan works by a different biological pathways than non-deuterated dextromethorphan. So those basic pharmacological differences may be important.

The other aspect of the study that was reported most recently with deuterated dextromethorphan that is different from what we're doing is the length of the trial. So that study was a 12-week trial and our study is a 5-week trial.

Interestingly enough previous studies with dextromethorphan and metabolic inhibitor either non-deuterated dextromethorphan or deuterated dextromethorphan did report very positive results with non-deuterated dextromethorphan and mixed results with deuterated dextromethorphan when those studies were conducted over a 5 or 6-week period.

So they are methodological differences also, which should be considered in interpreting the reported results versus for deuterated dextromethorphan versus what might be seen with AXS-05 where we’ve always been pretty confident in the rationale for AXS-05 in Alzheimer's disease agitation and we are looking forward to the results of our study, which we expect to have in the first half of next year..

That’s helpful added color [indiscernible] on Cedric. I had questions on AXS-07, but I’ve already taken enough time. So I will hop back in the queue..

And your next question comes from the line of Yatin Suneja with Guggenheim..

Hey, good morning, everyone. Thanks for taking my question. Just following up on the question that Charles asked earlier about the GEMINI enrollment.

I mean given that you enrolled the trials so rapidly, could you maybe talk about the steps that you might have taken to make sure that you enrolled the right patient population there is a notion that there are some of these professional patients, and maybe talk about the steps.

And then in terms of the baseline MADRS [indiscernible], could you maybe tell us what the cut off was for enrollment? Should we anticipate the average MADRS or [indiscernible] for GEMINI to be similar to ASCEND? Then I do have a follow-up..

Well, thank you, Yatin for the question. With regards to your -- the first part of your question, which just speaks to quality, we do agree that controlling quality and having a high-quality trial, having high-quality patient in the study is paramount.

And we were really proud of the conduct of the ASCEND trial where one of the things that we implemented was high quality control, including confirmation of patient diagnosis for the patients who are enrolled in the trial.

Now they are professional patients as you mentioned, which are out there, that’s the problem with all clinical trials and especially in the U.S. There are various measures which can be taken to minimize the enrollment of professional patients.

For example, there are patient databases, which help, but I think the other way to help to control not just for that, but to control for in a [technical difficulty] patients in general is to have some kind of third-party confirmation of the diagnosis of these patients.

And we did implement such a procedure in the ASCEND trial and we're replicating it in the GEMINI trial. And because we also had experience with ASCEND, we were able to even further enhance those measures. So GEMINI did enroll very quickly. We were aware that it might enroll quickly.

And so we put in place a lot of measures to ensure that quality was maintained along with the speed of enrollment. And with regards to just the demographics of the patients in the GEMINI trial from the baseline MADRS scores, I will turn it over to Cedric..

Yes, thanks, Herriot. The few points I would add is with our experience through the positive ASCEND study and STRIDE, we’ve established relationships with a clinical site. So there's a lot of what you would call good infrastructure there based on our prior experience.

And we wanted to make sure that the adjudication and judgment and confirmation of diagnosis in symptomatology was approached in the same way for the GEMINI study as we’ve done previously.

So in terms of the cut off, well-established cut off on the MADRS Total score of 25 points or higher allows one to identify patients who are moderate to severe severity. Again, that was the same as we’ve done previously in Ascend.

And third-party confirmation allows us to make sure that the patient demographic we are seeing similar age group, gets in on the [indiscernible] and the potential to recruit professional patients which of course we know can contribute to [indiscernible] readings and elevated placebo response.

So there have been a number of measures as Herriot mentioned that we implemented to ensure the quality of the patients coming into the trial [indiscernible] and that the integrity of this trial, just like the prior one is maintained..

Got it. And then just two more. Can you maybe comment on the NDA filing like to get a broad MDD label, what is needed? Do you have an agreement on the a set to get a blog MDD the label what is needed to you have an agreement on the FDA what would be the gating factors, if you have one of these ongoing trials positive.

And then just finally if you can also comment on the STRIDE-1, like what was the main reason to push the timeline into Q1 was it to enroll more patient or to build a safety database? But it seems like you hit the required number earlier in May. Thank you..

Sure. With regards to the requirements for an NDA filing, as you pointed out, the requirements are two positive trials. So should either the GEMINI or STRIDE be positive. Those positive results in conjunction with completed ASCEND trial would be sufficient to file an NDA.

So that was the result of the breakthrough therapy meeting which we had and which we previously reported on. In terms of the timeline for NDA filing, we are targeting finally an NDA assuming that we’ve success with one of these studies by the end of 2020.

With regards to the question around the timing of stopping screening in the STRIDE-1 trial, as a reminder, the reason why we continued screening beyond the target, beyond the target enrollment in the STRIDE-1 trial was to capture patients who have TRD into the safety database. That is a requirement for the NDA filing.

So the driving factor was to assure as robust as possible an NDA package without affecting the timeline to an NDA filing. We launched the open-label safety extension trial to capture those TRD patients in July and now we’ve a very good sense of the number of patients who have come out of STRIDE and who have gone into the open-label safety extension.

And given the increased interest in the STRIDE-1 trial recently and the number of patients who are in the queue, we felt that it was prudent to capture those patients to get to a target number, a target proportion of patients with TRD in the open-label safety extension.

Now the team, meaning the clinical team and the regulatory team gave this quite a bit of thought. And I'll turn it over to Cedric just to give you a little bit of color in terms of how we thought about the proportion of TRD patients should be in the safety database..

Yes. So to ensure that the NDA filing was as robust as possible, we wanted to capture a proportion -- an appropriate proportion of TRD patients that approach that what you see in the real world general MDD population. So as Herriot said, we [indiscernible] enrolled the study were approximately 300 subjects randomized in STRIDE.

And by screening enrolling until the end of November, this allows us to achieve the proportionate representation of TRD patients, which again reflects real-world approaches in the real world MDD population. Now importantly this does not change our timeline for the NDA filing in the second half of 2020.

And in fact only strengthens it, making it more robust..

And your next question comes from the line of Joon Lee with SunTrust..

Hi. Thanks for taking my question.

Regarding STRIDE-1 study that's now reporting in the first quarter of '20, given the continued recruitment into the study through the end of this month compared to the original plan, does that improved the powering of the study in any way? And also given STRIDE as an important study and that’s just because of the TRD study, but also because it -- has a significant amount of the safety database now if STRIDE-1 reach out negative, does that compromise the legitimacy of the safety database in any way and impact the NDA filing for MDD largely on this part.

Can you tell us about the proportion of the safety database is coming from ASCEND, GEMINI and STRIDE-1? Thank you..

Thank you, Joon for the question. With regards to what would happen if STRIDE were negative, as a reminder, should either GEMINI or STRIDE be positive that would allow us to file an NDA for MDD. So we are in a pretty advantageous position there with regards to optionality.

The difference, of course, would be that should STRIDE be positive that would be included, the data would be included in the product label. However just to be clear, the indication in either -- under either scenario would be for MDD.

Now with regards to the proportion of patients coming out of STRIDE versus GEMINI, that who are in the open-label safety extension trial, we’ve have not yet disclosed that exact percentage that is in flux.

But I think one thing that we can guide you to is the fact that, as Cedric mentioned, we currently are at 300 subjects who are randomized in the STRIDE-1 trial. And you had reached the target enrollment of about 250 subjects back in the second quarter.

And the -- yes -- and so the -- so that should give you a sense of how many patients potentially could have come out of STRIDE and entered into the open-label safety extension. Now to your very first question, around powering.

One of the results of over enrolling the study to capture additional STRIDE-1 patients or TRD patients into the open-label safety database is the fact that that there are more patients in the study who will be in the efficacy analysis. So, yes, so that would have the effect of increasing the power of the trial..

And I have a couple on the migraine as well. Correct me if I'm wrong, but for AXS-05 my understanding is that you have an open-label safety study ongoing with expected enrollment of up to 300.

Could you talk to me what the percentage of patients completing MOMENTUM are -- had that have rolled over into the open-label study?.

I don't know if we have an exact number yet, but we are capturing a fair number of the patients, who are exiting the MOMENTUM trial into the open-label safety extension. So we’ve not done the calculations, so we're not going to give you an exact number. But I think we’re capturing a significant percentage of those patients..

Okay. And very last question, help us understand what exactly is the difference between MOMENTUM and INTERCEPT, specifically it seems like you’re encouraging patients to take the AXS-07 as soon as they have symptom -- they notice the symptom of migraine.

So what's a typical lag between onset of migraine symptom before taking the drug in both studies, if that’s the goal?.

Yes. So, I will lead off and I will let Cedric provide some color. One overarching comment is that in typical acute migraine trials patients are required to wait until their pain reaches moderate or severe intensity prior to dosing. And so that's how the MOMENTUM trial is being conducted and in the INTERCEPT trial that is not the case.

So in the INTERCEPT trial patients are required to, or instructed to treat their migraine at the earliest sign of migraine pain. And so now interestingly enough that is how a specialist and clinician -- another clinicians who treat migraine patients instruct their patients to take acute treatments in the real-world setting.

So I will turn it over to Cedric, who can -- who will give you a little bit more color in terms of what we would expect to gain from INTERCEPT..

Yes. Thanks, Herriot and thanks for the question. I think the real distinction here is MOMENTUM being a registrational trial for the purposes of filing an NDA. And if positive, we would only need one study to prior quarter of treatment -- retreat migraines.

But what we see in the real-world and that’s real key term is real world, is that patients don’t want to wait till their pain becomes moderate to severe. And [indiscernible] physicians with [indiscernible] survey speaking to the fact that recognition believe that patients who are treated in migraine are the earlier sign of pain.

So in order to generate additional real-world data and to fully understand the potential kind of the utility of AXS offset in the treatment of migraine, we wanted to see exactly what it would look like in patients who are treated their migraine at the earliest kind of thing, we are excited to have that additional data generated through the interest input..

Thank you..

And your next question comes from the line of Marc Goodman with SVB Leerink..

Yes. Good morning. I was wondering if Dave could make some comments about joining the company. And obviously coming from a company that has a migraine through our guidance curiosu your thoughts about this migraine jug and how it's going to be positioned..

Yes. Well, good morning, Marc, and thank you for the question. I think, first of all, I couldn’t be more excited to join Axsome.

I think that when you look at kind of meaningful work that we all do, I’m proud to be surrounded by a team of professionals who kind of work day in and day out in the service of accelerating treatment options for people in need.

And certainly my most recent experience within the CNS category has been in migraine, I have prior experience in other CNS areas including depression. I think when I look at the potential for AXS-07, I’m tremendously excited.

And when you place it in the context of the marketplace, over the past year to two years we've seen greater focus on migraine that is certainly well-deserved not only with patients but with clinicians. And we are also seeing an elevation of treatment expectations.

And when we look at those treatment expectations, the information continues to point to what both patients and physicians are looking for in the acute treatment of migraine. And that’s consistently improved efficacy.

So when you look at the AXS-07 program it is fully designed to deliver just on that improved efficacy with not only speed of onset, but with degree of onset and the ability to hold that response longer. So sustain pain freedom.

And so when we look at that opportunity, I couldn’t be more excited about having a program or a trial in MOMENTUM where we're looking specifically at patients who have had a suboptimal response to prior therapies, and we're putting AXS-07 head-to-head against what is commonly viewed as one of the more effective acute agents and rizatriptan.

And that’s really what clinicians are looking for is improved efficacy and we have a head-to-head comparative trial that is going to give them the evidence to really make a solid clinical decision, and hopefully serve acute migraine needs much more sufficiently than what’s been done in the past. So I’m very excited about the opportunity for AXS-07..

Thanks. One other thing here, can you just tell us how given the TRD and the MDD studies are not really going to come out at the same time. Are you planning on putting out a press release on MDD before the end of the year.

And then on TRD early next year, is that kind of the plan with the separate press releases?.

So we are very confident in the top line results from the GEMINI trial in MDD by year-end team. The team is working very hard towards that, and it's completed an enrollment in the trial.

So we're very confident in that timeline, and not just the GEMINI trial, but also the CONCERT trial with AKS-12 in narcolepsy as well as the MOMENTUM phase 3 trial in the acute treatment of migraine. So all those studies, we are confident we will come out by year-end.

And with regards to TRD, we're also confident that this study will read out in the first quarter based upon the fact that enrollment has been completed and we know exactly when we're stopping screening. Allowing the patients who are currently in screening, in STRIDE to go through the trial which is our goal.

That would put data from STRIDE in the first quarter. We put last patient, last visit out in the middle of the first quarter which would imply data is sometimes they are after. So in the second half of the first quarter..

Thanks. And your next question comes from the line of Robert Hazlett with BTIG..

Yes. Hi, guys. This is Jake online for Robert. Thanks for the question. If I could just follow-up, I guess one more on STRIDE-1.

Just wanted to confirm If patient accrual and rollover into the open-label was in line with your expectations?.

Yes. Patient accrual and rollover into the open-label is in line with our expectations..

Okay. Thank you.

And then maybe this is a little bit early, but just taking two NDAs in the second half and next year, can you just comment on where you’re with establishing a commercial manufacturing supply chain?. Thank you..

So with regards to manufacturing, we're in excellent shape. We are conducting our Phase 3 trial with commercial supplies. So in other words, commercial scale up has already occurred. And there will be no need to transfer manufacturing once we file the NDA..

Thanks. Congratulates on the progress..

Thank you..

And your next question comes from the line of Robert Burns with H.C. Wainwright. Q - Robert Burns with H.C. Wainwright Hi, guys. Thanks for taking my questions. So my first one.

Just, Dave, probably a little sense to the feedback you’ve got from physicians as well as payers about the willingness to prescribe a drug like AXS-05 as frontline therapy and what kind of prior authorization or [indiscernible] programs might be applied ahead of AXS-05 deployment?.

So, we’ve got an excellent feedback on the profile thus far of AXS-05 in MDD. As you know, we did report out results from the ASCEND trial. Those results have been presented at various scientific conferences.

So that has a loud feedback from the KLL [ph] community and the broader physician community and it has been all very positive based upon the fact that the study did show a rapid onset of action for AXS-05 and also the fact that it was conducted versus an active comparator. So we're encouraged by that.

Clinicians also really like the fact that AXS-05 uses a new differentiated mechanism of action, which is an NMDA receptor antagonism, the fact that it is orally administered. So there is quite a bit of excitement we think from the clinicians who have seen the data and who looked at it.

And now a portion of the what we need to do is, we need to replicate those findings and we're looking to do that in the GEMINI trial and also in the STRIDE-1 trial. With regards the payers and [indiscernible], I think it's premature to have those discussions before we actually have full data on the product candidate.

But I will turn it over to Dave who will give just some top line thoughts..

Yes. And thank you for the question. When we think about AXS-05 and working with payers, I think kind of the foundational element in working with payers and determining access is really understanding the clinical profile. And as Herriot alluded, we still will be seeing much of those clinical data in the coming weeks.

But that is why I'm really excited about the way that we're conducting our clinical trials to provide the type of information that we think payers will utilize to make appropriate coverage decision.

And one could understand the specific patient types and patient populations where it might make sense to use AXS-07 as perhaps a first-line therapy -- I’m sorry, AXS-05 as perhaps a first-line therapy, but also given the fact that 70% of the time the first therapy fails the patient in depression, then certainly there is a robust population out there in which AXS-05 would be used after first line.

So we would work with payers directly to demonstrate the clinical utility, the specific patient population and then of course we always pull in the economic realities of effective treatment into those discussions as well..

And if I could just add the fact that for decades, the existing antidepressants have the same mechanism of action. So with the potential approval of AXS-05, we could potentially be the first novel mechanistic into the first oral in NMDA antagonist which would represent a new mechanism of action.

So I think it is also a compelling case to be made to provide a new mechanistic oral agent would have a place in first-line treatment for MDD..

Awesome. Thank you on that. And then just one more. So given that enthusiasm you guys have for AXS-05, [indiscernible].

What sort of pre-commercial preparations that you’re currently undertake in anticipation of the potential launch, if any of this [indiscernible]?.

Yes, I mean, I think when we look at pre-commercial efforts, a lot of those efforts around are making sure that we have the appropriate understanding of the marketplace, the appropriate understanding of the patient types that would most benefit, the appropriate understanding of the specific position to would be in the best position to serve those patients.

And I think that we want to make sure that there's a proper education out there in terms of not only the unmet need, but the potential for AXS-05 to help fulfill that need. So those would be some of the key things that we would think about..

Awesome. Thank you..

And your next question comes from the line of Myles Minter William Blair..

Hi, guys. Thanks for taking the question.

Just on MOMENTUM, I’m curious to know whether patients enrolled in that trial that any of them actually had an inadequate response to the triptan class in general or rizatriptan specifically? And also the documented inadequate response, does that mean that you are sort of in reaching for a patient population that might have nausea as a much bothersome symptom, this heard from a few docs that tends to be the most bothersome symptom that its most difficult to trade.

So any inadequate response might actually [indiscernible] reaching in that population, anything you could tell me there would be helpful..

So, Myles, thank you for the question. As a reminder all the patients who are enrolled, who are randomized into the MOMENTUM trial must have a history of inadequate response to prior acute treatments. And we confirm that using an instrument called the Migraine Treatment Optimization Questionnaire.

The -- that the prior acute treatment will vary amongst the patients. And so many of those patients will have been on triptan and their inadequate response will then be to triptan, but it could also been to other acute migraine treatments.

And in terms of the question around nausea and whether or not we are enriching for patients with that most bothersome symptom, I will turn it over to Cedric for any thoughts..

Thanks. So we're not enriching specifically around nausea, but I agree with your observation that sometimes patients who experience nausea is the most bothersome symptom are in fact we want to having adequate response. We haven’t looked into [indiscernible] in that way. Obviously, we are still running the trials.

But I think it's an astute [ph] observation that nausea may contribute to inadequate response. And we are looking forward to tacking that element of the patient [indiscernible]..

Okay. Thanks for that. And then, maybe follow on question for Dave. Just in -- the clinician interviews that you’re no doubt doing, did they have sort of difference of opinion when they’re looking at potentially prescribing 05 in depression as to whether GEMINI or STRIDE-1 that are positive or negative.

Have you looked into that scenario analysis? And also a history of the company paying very, very capital efficient and probably from what I’ve heard not going to use a massive neurology [indiscernible] if you could just give us some top-level on some unique marketing strategies that you might be thinking about that’s not going to save the SG&A if the company skyrocket, if you just got to market yourself?.

Yes. Well, Myles, thank you very much for the question. I think, first of all, when we look at our commercial efforts and certainly the sizing of commercial efforts there are a number of factors that will consider. So first of all, of course as we mentioned it starts with kind of what’s the clinical benefit of the therapies as we mentioned.

And then also looking at what are those specific patient audiences, whether that’s MDD or TRD, that we would be prepared for and then starting to look at the physicians that have the greatest potential to reach that target audience, and we would also look at what the prescriber kind of adoption patterns are.

And then we've also addressed kind of the reimbursement environment and that can have geographical implications as well. And then the other key component that I mentioned in my opening comments was really focused around efficiency.

When you look at kind of a CNS portfolio of products as well as indications, one of the things will be very keen to understand is where we can drive efficiencies across that portfolio to make sure that every dollar that we spent from a commercial perspective is really well directed towards ensuring that the appropriate patients actually receive the benefit of these therapies.

And then I think we also will look at not only personal promotion through highly qualified sales professionals, but what’s the right mix of reaching some of those target prescribers through non-personal promotion.

So when I size up the opportunity there are a number of factors that we will look for, but the general tenants will be to really understand our customers to the greatest level that we can, what their potential to reach our target audience, and then the most efficient and most effective ways in which we can reach them..

Got it. Thanks for the questions..

And your next question comes from the line of Matt Kaplan with Ladenburg..

Hi, guys. Good morning and congrats on the progress. Just wanted to dig in a little bit into the CONCERT study, AXS-12 for narcolepsy.

given the unique design in terms of crossover design, can you give us a sense in terms of what type of signal you’re looking for in terms of impact on cataplexy events in that study?.

Thanks, Matt, for the question. So as a reminder, the AXS-12 study in narcolepsy, it is a placebo-controlled trial. So it's a randomized, double-blind, placebo-controlled trial using a crossover design. It is a 20 patient trial, but because it uses a crossover design, it effectively provides the power of a 40 patient study.

Now the -- so in other words, roughly 20 patients per treatment arm. We are looking forward to see what the data show, but depending on -- if there is an effect and the magnitude of the effect, that design should put us in a good position with regard to measuring an effect on cataplexy.

One thing that we do point you to is, if you look at the prior trials in cataplexy, which were conducted with sodium oxybate in the package inserts, those studies had around 30 patients, 30 to 33 patients per treatment arm. So while although our trial is on the small size, we’re effectively around 20 patients per treatment arm.

So I don’t know if that gives you some sense, but depending on the effect, the magnitude of the effect if there is an effect, it would put us in a good position to be able to demonstrate that physically [ph]..

Okay. That’s very helpful. Thank you, Herriot..

And your next question comes from the line of Charles Duncan with Cantor Fitzgerald..

Hi, guys. Thanks for taking the follow-up. I had a follow-up on AXS-07 and the migraine base generally, probably for Dave and maybe Cedric. With regard to the evolving migraine space [indiscernible], obviously lots of activity in monoclonal antibody land, which you have experienced with, but also orals coming to market.

I’m just kind of wondering where you see the potential differentiation for 07? Would it be that you like to see efficacy in terms of magnitude of response relative to placebo, or speed of onset or durability? What do you think is the key thing that you like to show?.

So I will make some overarching comments just about the design of the trial just as a reminder and then -- will turn it over to Dave for some question -- sorry for some further thoughts. As a reminder, the way that the MOMENTUM trial is designed, we are enrolling patients who are difficult to treat. I think that's really important.

And the second point is that we do have the active comparator rizatriptan. And the way that -- the study is designed in order to meet the FDA's combination products rules is we’ve a key secondary endpoint of sustained pain freedom for the rizatriptan component.

So in other words, in order to show superiority to rizatriptan, we have to show superiority of AXS-07 to rizatriptan based on sustained pain freedom. So not only does the patient have to be pain-free two hours, but that pain freedom has to be maintained through 24 hours.

That gives you a sense of the potential benefits of AXS-07, one is just generally increased efficacy. And secondly, it's a reduction in Symptom recurrence, which we think it has a good rationale based upon the long plasma half-life of the meloxicam component. So that -- that’s how we think about it.

So coming out of the study if we do have success, what it will show will be the efficacy of AXS-07 in a difficult to treat patient population and potentially against an active comparator. So I will turn it over to Dave to talk about what that might mean in the marketplace..

Thank you, Herriot, and thank you for the question, Charles. I think when we look at our understanding of the marketplace, one thing that is very consistent is whether it is survey information from patients or from clinicians, there's a high degree of consistency in what the greatest unmet need in the marketplace is today.

And while there may be a lot of variables that have the potential to deliver on unmet need, overwhelmingly all the roads lead back to improved efficacy. Clinicians are looking for a greater percentage of success, meaning pain freedom when they’re prescribing for their patients.

And when you look at the trial design as mentioned by Herriot, the fact that we would have head-to-head data against what is largely considered one of the more effective therapy for acute treatment in a difficult to treat patient population, we think will give physicians tremendous confidence to satisfy that unmet need of how can we get better efficacy versus what I'm using today.

And I think that will be the pivotal data that will be most compelling not only for patients and clinicians, but even when we start to engage payers, because many new therapies that launched, don’t have that head-to-head comparison data with current standard of care.

And I think one thing that we don't talk as much about that many times gets overlooked is, this is also being delivered in the route of administration that patients and clinicians overwhelmingly prefer. So not only can you get the potential for improved efficacy, but you can do it in an oral administration.

And I think that is something that again the combination of improved efficacy against current standard of care as well as an oral administration we think makes this very compelling, and when we engage physicians with that type of a profile, it's not surprising to see their willingness to prescribe AXS-07 tremendously high..

Right. And like that 24 hour durability, efficacy measure could be a clear differentiator, but I’m wondering if you think about triptans generally and [indiscernible] they should not be used in patients with known or suspected cardiovascular risk.

Wondering if that has been a consideration in the development program and if you anticipate that that would still up in the label? And then final question is regarding a multi-dose safety study, I’m a little surprised that you don't have to do one for say 6 months or 9 months with intensive dosing or 12 months, excuse me.

Sure. So, Charles, thanks for the additional question. So AXS-07 it does combine MoSEIC meloxicam, so our MoSEIC technology would just be the absorption of meloxicam along with rizatriptan.

So because it does contain rizatriptan we would expect that any -- that the profile of rizatriptan in terms of many types of warnings that are on the current rizatriptan label would also make it into the label for AXS-07, should the product be approved.

With regards to the -- that the percentage of patients who are contraindicated against triptans because of cardiovascular factors, risk factors, it is interesting we did recently commission a survey of neurologists as well as other migraine treating physicians, and the survey was conducted by MEDACorp and the percentage of patients who currently are contraindicated for triptans was 12% from that survey [indiscernible] clinicians.

And we were comforted[ph] by that number since I think it roughly approximates with what you might have seen in a survey conducted by your firm, which I believes around 16%. So those values are pretty consistent. And with regards to the multi-dose question, our efficacy trials, so in other words, the MOMENTUM trial is a single dose study.

However, we are required to conduct a long-term safety study, which is ongoing. That study was launched in the beginning of July, and so patients are treated for up to 1-year. So they’re being treated for multiple attacks over that 1-year period..

Okay. That’s helpful. Thanks for all the added color and taking my follow-up questions..

And your final question comes from the line of Yatin Suneja with Guggenheim..

Hey, guys. Thank you for allowing a follow-up.

Just a real quick question that we are getting from investor, could you maybe comment on how many patient did you end up enrolling in GEMINI? And of the patient that you’re able to enroll, can you confirm how many have been validated by the independent assessor as to have a conform MDD diagnosis? Thank you..

So the GEMINI study targeted approximately 300 patients. And so we reached the -- we completed enrollment -- now you never end up with the exact number of patients that you target as you know. What we can say is that the study did reset number and surpass it. So we did over enroll somewhat the exact number.

Of course, we will provide in a few weeks when we announce the results of the trial and in terms of the percentage of patients who were evaluated by the independent assessor. So every patient that it is randomized, is evaluated through the -- through that process. And that's very important component of quality control of the trial.

And so -- I hope that answers your question..

Yes. Wonderful. Thank you so much..

Thank you..

And I will now turn it back over to Herriot..

Well, thank you. Thank you all for joining us on the call today. We -- just a public service announcement, we will be having an upcoming migraine key opinion leader conference call and webcast on November 25. And so we hope that you'll join us for that. That event will feature presentations from Dr. Richard Lipton as well as Dr. Stewart Tepper.

And it will focus on AXS-07 and the unmet needs in the acute treatment of migraine. The Axsome team is committed to developing differentiated medicines for difficult to treat CNS disorders. We look forward to reporting top line results from our clinical trials over the balance of the year..

And this concludes today's conference call. Thank you for your participation. You may now disconnect..