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Edited Transcript of AXSM earnings conference call or presentation 7-Nov-19 1:00pm GMT

Q3 2019 Axsome Therapeutics Inc Earnings Call

New York City Nov 9, 2019 (Thomson StreetEvents) -- Edited Transcript of Axsome Therapeutics Inc earnings conference call or presentation Thursday, November 7, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Cedric O'Gorman

Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs

* David C. Marek

Axsome Therapeutics, Inc. - Chief Commercial Officer

* Herriot Tabuteau

Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President

* Mark Jacobson

Axsome Therapeutics, Inc. - SVP of Operations & Secretary

* Nick Pizzie

Axsome Therapeutics, Inc. - CFO & Principal Accounting Officer

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Conference Call Participants

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* Charles Cliff Duncan

Cantor Fitzgerald & Co., Research Division - Senior Analyst

* Joon So Lee

SunTrust Robinson Humphrey, Inc., Research Division - VP

* Marc Harold Goodman

SVB Leerink LLC, Research Division - MD of Neuroscience & Senior Research Analyst

* Matthew Lee Kaplan

Ladenburg Thalmann & Co. Inc., Research Division - MD & Head of Healthcare Equity Research

* Myles Robert Minter

William Blair & Company L.L.C., Research Division - Analyst

* Robert John Burns

H.C. Wainwright & Co, LLC, Research Division - Associate

* Yatin Suneja

Guggenheim Securities, LLC, Research Division - MD & Senior Biotechnology Analyst

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Presentation

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Operator [1]

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Good morning, ladies and gentlemen, and welcome to the Axsome Therapeutics Third Quarter 2019 Financial Results Conference Call. (Operator Instructions)

As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, Senior Vice President of Operations at Axsome Therapeutics. Please go ahead.

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Mark Jacobson, Axsome Therapeutics, Inc. - SVP of Operations & Secretary [2]

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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 axsome.com.

During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety and intended utilization of our investigational agents, our clinical and nonclinical plans, our plans to present or report additional data, the anticipated conduct and 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 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 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; and Nick Pizzie, Chief Financial Officer, who will provide a financial update.

I'd now like to hand the call over to Herriot.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [3]

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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 have significantly advanced our 3 clinical stage CNS product candidates, which are being evaluated in 6 efficacy trials, including 5 Phase III trials and 1 Phase II trial across 5 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 in 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'd like to turn it over to Dave. Dave?

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David C. Marek, Axsome Therapeutics, Inc. - Chief Commercial Officer [4]

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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 an important data unveiled in the coming weeks and possibly lead to 2 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?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [5]

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Thank you, Dave. I will now provide an update on our programs and upcoming clinical milestones. Beginning with AXS-05, our novel, oral, investigational and NMDA receptor antagonist with multimodal activity. The AXS-05 is being evaluated in 2 Phase III depression studies. The GEMINI placebo-controlled trial of AXS-05 in major depressive disorder or MDD, and a STRIDE-1 active control 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 III active control trial of AXS-05 in TRD will conclude by the end of November. This approach allows for a 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 readouts 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, an 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 advanced Phase II/III 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 III 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 of Phase III placebo-controlled trial in which patients are to administer AXS-07 at the earliest 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 earliest 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 II 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 III GEMINI trial of AXS-05 in MDD, the Phase III MOMENTUM trial of AXS-07 in the acute treatment of migraine and a Phase II CONCERT trial of AXS-12 in the treatment of narcolepsy. We anticipate a continuation of significant milestones into next year with top line results from the Phase III STRIDE-1 trial of AXS-05 in TRD and the Phase III INTERCEPT trial of AXS-07 in migraine, both expected in the first quarter of 2020.

We also anticipate top line results from the Phase II/III trial of AXS-05 in Alzheimer's disease agitation in the first half of 2020, and potentially, 2 NDA filings for AXS-05 in MDD and for AXS-07 in migraine in the second half of 2020.

Now I'd like to turn the call over to Nick for a financial update.

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Nick Pizzie, Axsome Therapeutics, Inc. - CFO & Principal Accounting Officer [6]

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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 do not anticipate any new equity financings prior to the readout from our Phase III 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.

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Mark Jacobson, Axsome Therapeutics, Inc. - SVP of Operations & Secretary [7]

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

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Questions and Answers

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Operator [1]

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

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [2]

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Congrats, Herriot and team, to all the progress this quarter and this year. Been an interesting year, continue to be so. I 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 conduct a bit of that trial. How does the patient sample look relative to your expectation in terms of characteristics of the patients? And then in terms of the dropout rate that you had assumed?

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David C. Marek, Axsome Therapeutics, Inc. - Chief Commercial Officer [3]

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Well, thank you, Charles, for the question. As a reminder, one of the things that we try to do with the GEMINI trial was we tried to design that study to replicate the ASCEND trial as much as possible. I believe that we've achieved 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, it's early. The study enrolled quite rapidly. But I'll turn it over to Cedric to see if he has a sense of what the patient demographics might look like in between the 2 studies?

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Cedric O'Gorman, Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs [4]

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Yes. Thanks, Herriot. And so as you know, we worked very strong -- we're very keen to make sure that 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 of MDD, that their symptomatology was moderate to severe. And we're pleased to say that the conduct and the trials -- that what we've seen so far in terms of -- because you mentioned discontinuation, for example, that has been very similar to the ASCEND trials. So we're happy with the design and conduct, and I think that's about it.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [5]

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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 result out of arguably a mindshare competitor. With a deuterated form -- with a drug that contained a deuterated form of dextromethorphan. And I'm just kind of wondering what you think that says about either conducting studies in Alzheimer's agitation patients or even a drug containing dextromethorphan because that one didn't meet at some point and you would have anticipated that it did.

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

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [6]

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So as you pointed out, the study which you're referring to did use deuterated dextromethorphan as part of their product candidate, that was one of the components. And AXS-05, as you know, uses nondeuterated 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 it's metabolized or unintentionally, maybe the way that it interacts with CNS receptors.

There is preclinical data that has been published, which does indicate that deuterated dextromethorphan works via different biological pathways than nondeuterated 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 was a 12-week trial, and our study is a 5-week trial. Interestingly enough, previous studies with dextromethorphan and a metabolic inhibitor, either nondeuterated dextromethorphan or deuterated dextromethorphan did report very positive results with nondeuterated dextromethorphan and mixed results with deuterated dextromethorphan when those studies were conducted over a 5- or 6-week period. So there were 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're looking forward to the results of our study, which we expect to have in the first half of next year.

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Operator [7]

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

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Yatin Suneja, Guggenheim Securities, LLC, Research Division - MD & Senior Biotechnology Analyst [8]

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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 enroll the right patient population? There is a notion that there are some of these professional patients, so maybe talk about the steps. And then in terms of the baseline MADRS and HEMD, could you maybe tell us what the cutoff was for enrollment? Should we anticipate the average MADRS or HEMD for GEMINI to be similar to ASCEND? And then I do have a follow-up.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [9]

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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 patients 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 trials. Now there are professional patients, as you mentioned, which are out there, and that's a problem with all clinical trials, and especially in the U.S. There is measures, which can be taken to minimize the enrollment of professional patients. For example, there are patient databases which helped. But I think the other way to help to control, not just for that, but to control for inappropriate 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 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 assure that quality was maintained along with the speed of enrollment. Now with regards to just the demographics of the patients in the GEMINI trial based by MADRS scores, I'll turn it over to Cedric.

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Cedric O'Gorman, Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs [10]

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Yes. Thanks, Herriot. The two points I would add is with our experience through the positive ASCEND study and STRIDE, we have established relationships with clinical sites. 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 and symptomatology was approached in the same way for the GEMINI study as we have done previously. So in terms of the cutoff, well-established cutoff on the MADRS total score of 25 points or higher and allows one to identify patients who are moderate to severe severity. Again, that was the same as what we had done previously in ASCEND. And third-party confirmation allows us to make sure that the patient demographic we're seeing similar group get in and that you avoid the potential to recruit professional patients, which of course, we know can contribute to flow of bleedings and elevated placebo response. So there have been a number of measures, as Herriot mentioned, that we implemented to ensure that the quality of the patients coming into the trial is optimal and that the integrity of this trial, just like the prior one is maintained.

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Yatin Suneja, Guggenheim Securities, LLC, Research Division - MD & Senior Biotechnology Analyst [11]

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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 FDA? And what would be the gating factor, 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 patients or to build the safety database? Because it seems like you hit the required number earlier in May.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [12]

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Sure. With regards to the requirements for an NDA filing. As you pointed out, the requirements are two positive trials. So should either GEMINI or STRIDE be positive, those positive results in conjunction with the 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 what the timeline for an NDA filing, we are targeting finally an NDA, assuming that we have 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 enrollment in the STRIDE-1 trial was to capture patients who have TRD into the safety database. That is a requirement for the end -- 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 have 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 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 us 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 who should be in the safety database?

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Cedric O'Gorman, Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs [13]

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Yes. So to ensure the NDA filing was as robust as possible, we wanted to capture a proportion -- an appropriate proportion of TRD patients that approach that, which you see in the real world general MDD population. So as Herriot said, we've over-enrolled the study, we're 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 or approaches 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, making it more robust.

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Operator [14]

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

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Joon So Lee, SunTrust Robinson Humphrey, Inc., Research Division - VP [15]

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Regarding STRIDE-1 study that's now reporting in first quarter of '20. Given the continued recruitment into the study through the end of this month compared to the original plan, does that improve the powering of the study in any way?

And also, given STRIDE is an important study, not just because of -- it's a TRD study, but also because it has a significant amount of the safety database now is STRIDE-1 result negative. Does that compromise the legitimacy of the safety database in any way and impact the NDA filing for MDD? And lastly, on this part. Can you tell us what the proportion of the safety database is coming from ASCEND, GEMINI and STRIDE-1.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [16]

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Thank you, Joon, for the question. With regards to what would happen if STRIDE-1 were negative.

As a reminder, should either GEMINI or STRIDE be positive, that would allow us to file an NDA for MDD. So we're in a pretty advantageous position there with regards to optionality. The difference, of course, would be that should STRIDE be positive that, 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 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 we 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 enter it 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 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.

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Joon So Lee, SunTrust Robinson Humphrey, Inc., Research Division - VP [17]

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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 tell me what the percentage of patients completing MOMENTUM are -- had that have rolled over into the open-label study?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [18]

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I don't know if you 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 have 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.

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Joon So Lee, SunTrust Robinson Humphrey, Inc., Research Division - VP [19]

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Okay. And the very last question. Help us understand what exactly is the difference between MOMENTUM and INTERCEPT, specifically. Now it seems like you're encouraging patients to take the ASX-07 as soon as they have symptoms, they notice the symptom of migraine. So what's the typical lag between onset of migraine symptom before taking the drug in both studies, if that's the goal?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [20]

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Yes. So again, I'll lead off, and I'll 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 other clinicians who treat migraine patients, instruct their patients to take acute treatment in the real world setting. So I'll turn it over to Cedric, who will give you a little bit more color in terms of what we would expect to gain from INTERCEPT?

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Cedric O'Gorman, Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs [21]

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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 file for the acute treatment of migraines. But what we see in the real world, and that's the real key term here is real world, is that patients don't want to wait until their pain becomes moderate to severe and neither do physicians with managed service, speaking to the fact that clinicians believe that the patients treat their migraine at the earliest sign of pain. So in order to generate additional real world data and to fully understand the potential clinical utility of AXS-07 in the treatment of migraine, we wanted to see exactly what it would look like in patients who treated their migraine at the early sign of pain. We're excited to have that additional data generated through the INTERCEPT trial.

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Operator [22]

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

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Marc Harold Goodman, SVB Leerink LLC, Research Division - MD of Neuroscience & Senior Research Analyst [23]

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I was wondering if Dave could make some comments about joining the company, and obviously, coming from a company that has a migraine drug, I was curious, your thoughts about this migraine drug and how it's going to be positioned?

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David C. Marek, Axsome Therapeutics, Inc. - Chief Commercial Officer [24]

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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 works 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 had 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 a greater focus on migraine that is certainly well deserved, not only with patients but with clinicians. And we're 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 sustained 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 in rizatriptan. And that's really what clinicians are looking for is improved efficacy, and we have a head-to-head comparative trial that's 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.

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Marc Harold Goodman, SVB Leerink LLC, Research Division - MD of Neuroscience & Senior Research Analyst [25]

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One other thing, Herriot. Can you just tell us now given that 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, there will be separate press releases?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [26]

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So we're very confident in top line results from the GEMINI trial and MDD by year-end. So the team is working very hard towards that. We've completed enrollment in the trial. So we're very confident in in that timeline. And not just the GEMINI trial, but also the CONCERT trial with AXS-12 in narcolepsy as well as the MOMENTUM Phase III trial in the acute treatment migraine. So all those studies that we're confident wIll come out by year-end. And with regards to TRD, we're also confident that, that 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. It would put last patient, last visit out in the middle of the first quarter, which would imply data sometimes thereafter. So in the second half of the first quarter.

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Operator [27]

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

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Unidentified Analyst, [28]

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This is Jake on the line for Bert. If I could just follow-up, I guess, one more on STRIDE-1. I just wanted to confirm if patient accrual and rollover into the open-label was in line with your expectations?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [29]

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

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Unidentified Analyst, [30]

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Okay. And maybe it's a little bit early, but just thinking 2 NDAs in the second half of next year. Can you just comment on where you are with establishing a commercial manufacturing supply chain?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [31]

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So with regards to manufacturing, we're in excellent shape. We are conducting our Phase III trials 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 NDA.

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Operator [32]

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And your next question comes from the line of Robert Burns with H.C. Wainwright.

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Robert John Burns, H.C. Wainwright & Co, LLC, Research Division - Associate [33]

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So my first one. Just based -- I just want to get a little sense as to the feedback you've gotten from physicians as well as payers about the willingness to prescribe a drug like AXS-05 as frontline therapy? And what kinds of prior authorization or step edit programs might be applied ahead of AXS-05 deployment?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [34]

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So we've gotten 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 allowed feedback from the KOL community and the broader physician community, and it has been very positive based upon the fact that the study did show a rapid onset 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 and differentiated mechanism of action, which is an NMDA receptor antagonism and the fact that it is orally administered. So there is quite a bit of excitement, we think, from the clinicians who've seen the data and who've looked at it. And now, of course, 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 to payers and step edits, I think it's premature to have those discussions before we actually have a full data on the product candidate. But I'll turn it over to Dave, who will give just some top line thoughts.

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David C. Marek, Axsome Therapeutics, Inc. - Chief Commercial Officer [35]

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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 are conducting our clinical trials to provide the type of information that we think payers will utilize to make appropriate coverage decisions. 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 -- or 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.

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Cedric O'Gorman, Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs [36]

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If I could just add the fact that for decades, the existing antidepressants have had the same mechanism of action. So with the potential approval of AXS-05, we could potentially be the first novel mechanistic and the first oral NMDA antagonist, which would represent a new mechanism of action. So I think there's also a compelling case to be made for why a new mechanistic oral agent would have a place in first-line treatment for MDD.

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Robert John Burns, H.C. Wainwright & Co, LLC, Research Division - Associate [37]

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Awesome. And then just one more. So given that enthusiasm you guys have for AXS-05 as well as the physician community. What sorts of precommercial preparations that you currently are undertaking in anticipation of the potential launch, if any, at this point?

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David C. Marek, Axsome Therapeutics, Inc. - Chief Commercial Officer [38]

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Yes. I mean, I think when we look at precommercial efforts, a lot of those efforts around 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 physician who would be in the best position to serve those patients. And I think that we want to make sure that there's the 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.

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Operator [39]

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

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Myles Robert Minter, William Blair & Company L.L.C., Research Division - Analyst [40]

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Just on MOMENTUM. I'm curious to know whether patients enrolled in that trial -- have 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're sort of in routine for a patient population that might have nausea as the most bothersome symptom? I've just heard from a few docs that, that tends to be the most bothersome symptom that is most difficult to treat. So any inadequate response might actually be enriching in that population? Anything you could tell me there would be helpful.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [41]

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So Myles, thank you for the question. As a reminder, all the patients who are enrolled were 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 prior acute treatment will vary amongst the patients. And so many of those patients will have been on triptans, and their inadequate response will have been to triptans, but it could have also been to other acute migraine treatments. And in terms of the question around nausea and whether or not we're enriching for patients with that most bothersome symptom, I'll turn it over to Cedric for any thoughts.

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Cedric O'Gorman, Axsome Therapeutics, Inc. - SVP of Clinical Development & Medical Affairs [42]

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Thanks a lot. So we're not enriching specifically around nausea, but I agree with your observation that sometimes it's the patients who experience nausea as the most bothersome symptom are in fact the ones who have inadequate response. We haven't looked into the data in that way. Obviously, we're still running the trials. But I think it's an astute observation that nausea may contribute to an inadequate response. And we're looking forward to tackling that element of update the patient need also.

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Myles Robert Minter, William Blair & Company L.L.C., Research Division - Analyst [43]

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Okay. And then maybe a follow-on question for Dave. Just in the clinician interviews that you're no doubt doing, did I have a sort of difference of opinion when they're looking at potentially prescribing 05 in depression as to whether GEMINI or STRIDE-1 read out positive or negative? And have you looked into that scenario analysis? And also a history of the company being very, very capital efficient and probably, from what I've heard, not going to use a massive neurology sales force. 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 see the SG&A of the company skyrocket if you do have to go-to-market yourself?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [44]

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Yes. Well, Myles, thank you very much for the questions. 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 we'll 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've 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 we'll be very keen to understand is where we can drive efficiencies across that portfolio to make sure that every dollar that we spend 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 nonpersonal promotion. So when I size up the opportunity, there's a number of factors that we'll look for. But the general tenets will be to really understand our customers to the greatest level that we can, what's their potential to reach our target audience and then the most efficient and most effective ways in which we can reach them.

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Operator [45]

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

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Matthew Lee Kaplan, Ladenburg Thalmann & Co. Inc., Research Division - MD & Head of Healthcare Equity Research [46]

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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?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [47]

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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're 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 can 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 statistically.

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Operator [48]

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

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [49]

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I had a follow-up on AXS-07 and the migraine space generally, probably for Dave and maybe Cedric. With regard to the evolving migraine space, obviously, lots of activity in monoclonal antibody land, which you have experience 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'd 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'd like to show?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [50]

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So I'll make some overarching comments just about the design of the trial just as a reminder, and then we'll turn it over to Dave for some questions. I'm sorry, for some further thoughts. Just 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 have a key secondary endpoint of sustained pain freedom or 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 for 2 hours, but that that pain freedom has to be maintained through 24 hours. Now 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 as good rationale based upon the long plasma half-life of the meloxicam component. So that's 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'll turn it over to Dave to talk about what that might mean in the marketplace?

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David C. Marek, Axsome Therapeutics, Inc. - Chief Commercial Officer [51]

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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 is 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 therapies for acute treatment in a difficult-to-treat patient population, we think it 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 launch 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.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [52]

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I like that 24-hour durability efficacy measure could be a clear differentiator. But I'm wondering, if you think about triptans generally and a view that 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 show 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.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [53]

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Sure. So Charles, thanks for the additional question. So AXS-07, it does combine MoSEIC meloxicam, so our MoSEIC technology, which just speeds the absorption of meloxicam along with rizatriptan. So because it does contain a triptan, we would expect that any -- that the profile of rizatriptan in terms of any 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 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 according to clinicians. And I -- and we were comforted by that number since I think it roughly approximates what you might have seen in a survey conducted by your firm, which I believe is around 16%. So those values are pretty consistent. And with regards to the multi-dose question. Our efficacy trials, so in other words, that 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 are being treated for multiple attacks over that one-year period.

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Operator [54]

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

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Yatin Suneja, Guggenheim Securities, LLC, Research Division - MD & Senior Biotechnology Analyst [55]

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Just a real quick question that I've been getting from investors. Could you maybe comment on how many patients did you end up enrolling in GEMINI? And of the patients that you are able to enroll, can you confirm how many have been validated by the independent assessor as to have a confirmed MDD diagnosis?

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [56]

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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 reach that number and surpassed 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 is randomized is evaluated through that process. And that's a very important component of the quality control of the trial. And so I hope that answers your question.

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Operator [57]

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And I'll now turn it back over to Herriot.

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Herriot Tabuteau, Axsome Therapeutics, Inc. - Founder, Chairman, CEO & President [58]

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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 Leaders Conference Call and Webcast on November 25. And so we hope that you will join us for that. That event will feature presentations from doctors, 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. Now 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.

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Operator [59]

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