Good morning, ladies and gentlemen. And welcome to the Axsome Therapeutics Conference Call. Currently, all participants are in a listen-only mode. Later, there will be a question-and-answer session and instructions will follow at that time. Accompanying slides are available for this presentation on the company website at axsome.com. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, Chief Operating Officer at Axsome Therapeutics. Please go ahead.

Thank you, operator. Good morning and thank you all for joining us on today's conference call. Our earnings press release providing a corporate update and details of the company's financial results for the first quarter of 2020 crossed the wire a short time ago and is available on our website at axsome.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety and intended utilization of our investigational agents, our clinical and non-clinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development and possible intended use of cash and investment. These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date and the company disclaims any obligation to update such statements. Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Dave Marek, Chief Commercial Officer; and Dr. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs. Herriot will first provide an overview of the company including reviewing recent developments and upcoming milestones. Following Herriot, Nick will review our financial results. We will then open the line for questions. I shall now turn over the call to Herriot.

Thank you, Mark. Good morning, everyone. And thank you all for joining Axsome Therapeutics first quarter 2020 financial results and business update conference call. Over the past several months, we have accelerated our evolution into a leading CNS company. During this time, we continued to advance our broad and deep late stage portfolio of novel differentiated medicines targeting difficult-to-treat CNS indications that have limited or no treatment options and that affect significant patient populations. We now believe we have one of the most robust CNS pipelines in the industry. Our late stage CNS pipeline is not only broad, but also proven as we have now generated or announced positive efficacy results from well controlled clinical trials in five different indications, including depression, Alzheimer's disease agitation, migraine, narcolepsy and fibromyalgia. Overall, these conditions affect more than 60 million patients in the US alone. The prevalence, seriousness of and high unmet needs represented by these conditions underscore the importance of our investigational medicines and the clinical data generated with them thus far. The resulting opportunities are significant. On this slide is a snapshot of select indications in our late stage pipeline for which we now have positive efficacy data from controlled clinical trials. For our AXS-05 product candidate, we announced positive NDA enabling results in major depressive disorder in December, showing rapid and substantial improvement in depressive symptoms. And last week, we announced positive results from our pivotal ADVANCE-1 trial of AXS-05 in Alzheimer's disease agitation, which similarly demonstrated rapid and substantial symptom improvement in this condition. We have also announced positive NDA enabling results in migraine with our AXS-07 product candidate, demonstrating superior efficacy. And last month, we announced positive results from our INTERCEPT trial of AXS-07 in the early treatment of migraine. Our AXS-12 product candidate for narcolepsy has demonstrated…

Thank you, Herriot. And good morning, everyone. I will focus on key highlights in the quarter and provide some financial guidance. We ended the quarter in a strong financial position that is consistent with our ability to rapidly advance our clinical programs and commercial preparations, while maintaining highly efficient fiscal management. R&D expenses were $27.5 million for the quarter ended March 31, 2020 versus $7.6 million for the comparable period in 2019. The quarter included a one-time charge of $10.2 million related to the upfront costs associated with the Pfizer licensing agreement, of which $7.2 million was non-cash related. Net of the costs related to the Pfizer licensing agreement, R&D expenses were $17.3 million. The increase versus the first quarter of 2019 was due to significantly more clinical trial activity during this most recent period, including the STRIDE-1, INTERCEPT, and ADVANCE-1 trials, the AXS-05 and AXS-07 open label safety studies, and to close out costs for our CONCERT, GEMINI and MOMENTUM trials. All of these trials, aside from the AXS-05 and AXS-07 open label safety studies, have now been concluded and are in the process of being closed out. G&A expenses were $5 million for the quarter ended March 31, 2020 and $2.8 million for the comparable period in 2019. The change is primarily due to increase personnel costs, mainly from higher stock compensation expense, along with the build-out of the commercial function. We ended the first quarter with $197.3 million in cash compared with $220 million at the end of the fourth quarter. We believe that our current cash position is sufficient to fund our anticipated operations based on our current operating plan for at least two years. That concludes our first quarter 2020 financial review. I will now hand the call back to Mark to lead the Q&A discussion.

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

[Operator Instructions]. And your first question comes from Charles Duncan with Cantor Fitzgerald.

Hey. Good morning, Herriot and team. Congrats on the clinical successes in the last 12 weeks and 12 months. And thanks for taking the questions. I had a couple of questions with regard to the NDAs for 05 in MDD and 07 in migraine. I wondered what are the rate limiting steps for the March 2 NDA filing. Is there any new clinical data, including safety exposure or CMC activities? And are these steps – would you characterize them as experimental or box checking milestones?

Thank you, Charles, for the questions. The rate-limiting steps, really, from a time perspective, would be our open label safety extension trials. We do need 300 patients treated for six months and 100 patients treated for one year for each product candidate. This is for AXS-05 as well as AXS-07. And we do expect to have those studies completed in the third quarter to put us on track to file our NDAs in the fourth quarter. With regards to CMC activities, there are registration batches which are being manufactured now. A good thing for us is that we have been manufacturing our clinical trial supply at commercial scale and also at the same CMO that we're using for commercial production. So, there's no scale up that needs to be done. Now, with regards to manufacturing and any kind of science to it, there's always tweaks and experimentation, but I would say that there is no rate-limiting step and there is no extensive experimentation. This is simply manufacturing our registration batches for regulatory purposes.

And, Herriot, would you schedule a pre-NDA meeting before either of those two, the safety or CMC activities, are completed?

Pre-NDA meetings are standard. And also, they're recommended. And so, yes, the pre-NDA meetings for both AXS-05 and AXS-07 are part of our process.

Okay. And then, just one last question. You very nicely outlined, call it, the market opportunity for these two candidates in the United States. And it's substantial. But when I think about the challenges with the indications that you're seeing, I'm kind of wondering if, first of all, that market opportunity may grow certainly with the impact of COVID in psychiatry, but also I'm particularly curious about what your thoughts are with regard to ex US commercial strategies. Would you consider out-licensing or what are your current thoughts there?

With regards to the effect of the COVID-19 pandemic on our market opportunities, unfortunately, the measures that have been put in place, which includes social distancing, as well as sheltering in place, are key risk factors for depression. And, in fact, an increased incidence of depression has been documented and has been reported from various sources. So, unfortunately, that is a reflection of the current environment that we're in. Now, with regards to market opportunities outside of the US, we do think that they are significant. You're correct that the sales potentials that we outlined – and we did this just to give folks a sense of the number of patients whose lives we could impact. Those numbers are just for the US, and Axsome does maintain worldwide rights through our product candidates. As part of our strategy, we stated that our corporate strategy is to license our product candidate outside of the US. So, that is part of our strategy and that is part of our ongoing activities.

Okay. Look forward to increased visibility on that probably over the course of the year. So, appreciate you taking my questions. Congrats on the progress. It's going to be an eventful year for you.

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

Hey, good morning. I was just curious, as you're thinking about commercializing the migraine drug, what are your thoughts on how the oral CGRPs have played out so far and what you're considering doing advertising DTC on the television to be able to compete with them?

Thanks, Marc, for the question, and I'll turn that over to Dave.

Hey. Good morning, Marc. Thanks for joining us this morning. Well, I think the uptake of the oral CGRPs has been strong. And I think that helps to speak to the unmet need out there that there is a marketplace that is still searching for therapies that go beyond traditional triptans to meet additional needs that patients have. And I think when you look at AXS-07, I think we fare very well in terms of our differentiated profile with the data that we have direct head to head with rizatriptan. So, we feel good about how the market is reacting to new acute therapies. I'm not completely surprised, as I mentioned, given the unmet need. Regarding consumer and direct-to-consumer advertising, I think there are a number of ways to engage with consumers. TV is one of the ways that we can engage with consumers. I don't think we're at a point where we'll take any options off the table. But when I think of engaging with consumers, one of the benefits of electronic engagement is we have more specific data around those customers you can engage electronically. And we can make sure that those that we engage with are kind of qualified in terms of where they are in their treatment journey. So, we won't take any options off the table this early, but certainly we would look to engage consumers. To the extent that we would use TV, we'll see where that goes. But we would lean more towards electronic means as the most efficient means to reach them.

Thanks.

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

Hi, guys. Thanks for taking my questions. And congrats on the progress. I have a question on Alzheimer's disease agitation. Do you plan to seek accelerated path to market similar to what Acadia did for Nuplazid based on a single Phase III? And if so, what do you need to prepare for that meeting? And along with that, do you feel the FDA of today is more or less accommodative than the FDA of five years ago? Thank you.

Thanks for the question, Joon. We're very excited about the results in Alzheimer's disease agitation. And I think what underlies your question is the clinical need there. And it is true that this is an indication for which nothing is approved. The unmet need, as well as the public health need there is high because these patients do need to be treated. And the alternatives that are out there currently are contraindicated or certainly advised against with FDA black box warnings against their use in this population. So, we feel that our pivotal Phase II/III ADVANCE trial results are strong. And what we're looking to do as quickly as possible is to meet with the FDA, and we need to have those discussions with the FDA. Our base case scenario, though, is that we would be conducting one additional trial. That has always been our assumption. And that is the usual FDA path. Now, as you're pointing out, there have been instances in the past where the FDA has approved products such as pimavanserin with one positive pivotal trial in indications which nothing is approved. However, I just want to pace it that that is not the way to run a business. It's not to hope for the best, but it's to plan for the most likely scenario. And that's what we've done. And we think that there certainly is a way to accelerate the approval of AXS-05 in this indication given what we currently know. So, we'll know more once we meet with the FDA, and we're looking to do that as expeditiously as possible. In terms of whether or not the FDA is more accommodating now than it was five years ago, I won't comment on that. We are a young company. So, we don't have the same history as some other companies, and it will probably be more appropriate to ask them to answer that question.

Thank you for the clarification. I just have one more follow-up. You have a very high class problem of having to meet with the FDA for many programs. You have listed seven meetings with the FDA in just the second half of 2020. Are you actually going to have seven separate meetings? Or will you have maybe two to three meetings to discuss multiple programs simultaneously? Just curious from a disclosure standpoint on when we can hear back on the FDA feedback if that is your plan to share the updates as you get the feedback. Thank you.

So, Joon, I don't know we've listed seven FDA meetings. Just in terms of interaction with the FDA, we do have a number of programs that are ongoing, which is true. And we also do have breakthrough therapy designation for AXS-05 in major depressive disorder and fast track designation for treatment-resistant depression and Alzheimer's disease agitation. So, those designations are important because they allow more frequent communications with the FDA. And so, certainly, there are a lot of interactions. And what we've done in the past is, when our interactions do lead to a development which is material, such as a change in – in terms of timing, then we have talked about that, we share that with investors. So, we plan to follow the same playbook. And certainly, anything that we think is material or that is a significant one way or the other, we would communicate expeditiously with the Street.

Thank you very much.

And your next question comes from Yatin Suneja with Guggenheim Partners.

Hey, guys. Good morning. Thank you for taking my question. Just a couple. On the filing, do you expect priority review for 05 and 07? And then, can you comment if there is any impact on the ongoing safety study or the long-term extension study because of COVID? Then I have a follow-up.

For AXS-05 in major depressive disorder, because we have breakthrough therapy designation, it is eligible for six-month review. So, we will certainly be seeking that. That's a decision that is made, though, typically after the NDA is filed, but, certainly, that is one of the features of a breakthrough therapy designation. For AXS-07, we do currently anticipate standard review. And in terms of the impact of COVID-19 on the ongoing open label safety extension trials, currently, we're not anticipating a significant impact, largely because a significant number of patients have already been enrolled in those studies. For each of the open label studies, for 05 and 07, the goal is to have 600 patients treated for three months and 100 patients treated for one year, and we currently have north of 700 or 800 patients in each of those studies. One of the aspects of clinical trials, which is most impacted by COVID, has to do with patients not being able to or not wanting to go to the clinical trial sites for their visits. Those visits are less frequent in long-term safety extension trials. So, that benefits us. And the other reason why patients typically need to go to clinical trial sites is to get drug supply. And we do have alternatives in place to make sure that drug supply gets to patients in their homes should they choose not to leave their homes.

Got it. And then, with regard to the TRD study that you plan to initiate, could you talk about the timeframe for completion? We understand this is not going to be a study similar to the STRIDE-1 that took a lot longer, but just help us understand a timeframe that we should be thinking about and the preparation that you might already be doing in anticipation of starting that study relatively soon.

We anticipate the timeframe from completing that second TRD study will be shorter than the timeframe that we experienced in completing the first TRD study. And we'll know more once we nail down the exact design of that trial and once we do some more internal projections. And we'll sort of share our thoughts once they're crystallized with the Street.

All right. Thank you very much.

And your next question comes from the line of Ram Selvaraju with H.C. Wainwright.

Hi. Thanks very much for taking my questions. Firstly, just wanted to see if you could reconfirm that the Phase III confirmatory treatment-resistant depression study with AXS-05 is going to be placebo controlled.

So, Ram, we're still finalizing the design of that study, but that is certainly one possibility. And once we finalize that design and confirmed it through discussions with the FDA, we'll let you know.

Okay, great. And can you comment on or give us an update on the status of AXS-05 smoking cessation. With all the shots on goal that you currently have, it seems like maybe you might be thinking about prioritizing other things, but just wanted to get a sense of how you're thinking about that at this time.

We're excited about the smoking cessation opportunity. A very large patient population, and probably the largest patient group that we're targeting with our various product candidates in the various indications. And our goal is to meet with the FDA, discuss the next steps in the smoking cessation program. So, that is one of our milestones for this year.

Okay, great. And then, on esreboxetine, I was just wondering whether you had gotten the chance to talk to the agency about what else they expect to see, what else they will need from you guys to potentially countenance the approval of esreboxetine in fibromyalgia and if you've gotten a sense from them as to what additional clinical data would be needed for you to generate.

Ram, we have not yet met with the FDA to discuss AXS-14. That is also one of our stated corporate goals for this year. So, we do expect that that will happen. And we're looking forward to discussing the data package which has already been generated. And that data package, as a reminder, includes a positive Phase III and positive Phase II trial.

Okay. And then, just lastly, on the narcolepsy program, I was wondering if you could give us your thoughts on the nature of the competitive landscape for AXS-12, particularly in light of the recent Phase III data on FT-218 and how you see FT-218 as competitive entrant. Obviously, it looks like that's going to be scheduled. AXS-12 is not going to be scheduled. But if you had any thoughts there, that would be helpful. Thank you.

So, this is an area of high unmet medical need where patients need new treatment options. FT-218, our understanding is it still has the active ingredient as Xyrem. So, we do think that it would be beneficial to have other molecules that work differently and that are dosed dramatically differently, such as AXS-12. Now, with regards to AXS-12, what we like about that product candidate is that it had a positive effect across a range of narcolepsy symptoms, not just cataplexy, but excessive daytime sleepiness. It also positively affected cognitive function. And, as a reminder, the product is very well tolerated. It is daytime dosing. And we do not expect to be scheduled, which would be another point of differentiation from the current product which is currently approved for cataplexy. And certainly, we think that that feature, in addition to the broad range of symptom improvement, would be welcomed by patients and clinicians.

Great, thank you very much. And congrats on all the progress once again.

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

Yes, thank you. Just one or two clarifying points. One is, with regard to AXS-05 in Alzheimer's disease agitation, that seems to us to be very important data. Not that MDD and TRD is not important with that molecule, but that, given the unmet need, is important. Is there a chance for breakthrough designation? And then, specifically, when do you intend to meet with the FDA? And then, with regard to that indication, could you do a little bit more to frame the opportunity? The unmet need is material here. What is the state of treatment? Are they treated with off-label benzos or atypical antipsychotics still, even with the black box? Just a little bit more about the opportunity, in addition to kind of the timetable with regard to your interactions with FDA would be helpful. Thank you.

Thanks, Bert, for the question. I'll let Cedric talk about the treatment landscape and then I'll answer the questions around FDA interactions.

Bert, at the moment, there's absolutely no approved treatment for agitation associated with Alzheimer's disease. It's highly prevalent and highly disabling and associated with increased mortality, accelerated cognitive decline, earlier institutionalization and death. And there's a real need. So, currently, physicians and prescribers and healthcare staff at nursing homes are resorting to have to use off-labels cause prescriptions of anti-psychotic drugs, which as you point out have the black box warning around use in the elderly. But it emphasizes the tremendous need that people are still resorting to these antipsychotics despite their own association with increased mortality, morbidity, cardiovascular problems and stroke. So, there's definitely a need for any treatment, first of all, and a need for an approved treatment which has not yet been achieved.

And with regards to the timing of FDA interactions, we are seeking to meet with the FDA as quickly as possible on this. There is, of course, always a lag from requesting a meeting to getting a meeting, but this is a priority. We do agree that these are important data. And we'll have more to say once we interact with the agency.

Okay, thank you.

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

Hey. Good morning, guys. And thanks for taking the questions. Just wanted to dig in a little bit more to AXS-12 for narcolepsy. What's your current sense in terms of the Phase III design that you plan to launch later this year? And do you expect that you would have to do, I guess, two Phase III studies or could one be sufficient?

Thanks for the questions, Matt. With regards to narcolepsy and the Phase III design, we've not yet finalized the design. However, it will incorporate a lot of the elements from our successful Phase II trial. So, in terms of the endpoint, certainly. And one difference will be that the Phase II was a crossover study and we would anticipate that this would be a parallel group study. And then, we are planning on conducting two Phase III trials and we would conducting them simultaneously.

Okay, that's very helpful. Thanks for the detail.

And your next question comes from Myles Minter. And, sir, would you please state your company name?

Sorry, must have got off. It's Myles Minter from William Blair. Thanks for taking the questions. The 800 patients that you've currently got enrolled or dosed in your open label extension safety of AXS-05, I'm just wondering whether you've got any more clarity or intend on talking with the FDA about the proportion of patients that would have to be TRD versus MDD for that single safety trial to serve as both the long-term safety database for both of those indications. So, theoretically, you wouldn't have to run another one on the end of the next TRD trial.

So, thanks for questions, Myles. So, as you know, that open label safety extension study does improve patients with both TRD and MDD. And in terms of the exact proportion, that's never been stated clearly one way or the other by the FDA. Now, what we've talked about is the way that we're thinking about it. And the way that we're thinking about it is to have a number of patients with TRD in the long-term portion of the trial, meaning those who have been treated for one year. That reflects the general proportion of TRD patients as compared to MDD in the general treatment population. So, that was our thinking. And then, with regards to the MDD trial, certainly, it probably becomes less relevant for that indication. And by the time that we do file for TRD, once that study is completed, as a reminder, we'll have then significantly more patients with TRD in our overall safety database.

That's helpful. And then, actually, on the TRD proposed trial, I know the design is yet to be definitively clarified. But if it placebo controlled and patients would theoretically have to fail two or more prior antidepressants, are you looking to control bupropion use in those patients?

So, just as a reminder, in the STRIDE-1 trial, all the patients were treated with bupropion. And now, certainly, it would make sense that, if we do have a study whereby we are dosing AXS-05 that we would restrict bupropion use. That makes sense. That is typical practice in any clinical trial whereby you would restrict additional use of the product or – of the active ingredients that you're testing. So, that's right now our preliminary thought. However, we are, as you know, finalizing the design of that trial and finalizing the design of studies. It takes into account a lot of important details. And we want to make sure that we think about those very carefully. And once we have the final design of the studies, we'll be able to provide you more detail.

Yes. So, I guess, the question was more about in the prior history of these patients, would you look at restricting bupropion use prior to enrollment? I know the trial will be monotherapy per se, but, yeah, if you were looking at the patient history and maybe looking at controlling prior bupropion use coming into the trial.

Right now, we would not anticipate controlling prior bupropion use just as we did in the STRIDE-1 trial where that was considered to be – or that was allowed to be – not just allowed to be, but it was mandated by the trial design for there to be one of the prior antidepressant failures.

Okay, cool. And then final one for me, just on AXS-12, just curious how the Pfizer licensing deal – when you got in AXS-14 for fibro, what that sort of extended clinical and non-clinical database would do in terms of maybe reducing the safety database that you would have to build for this narcolepsy treatment after a pivotal trial? Is there any additional color there?

It certainly helped us, the patient safety database with [indiscernible] and esreboxetine, which we licensed from Pfizer [indiscernible] thousands of patients who have been exposed for various lengths of time. So, those patient numbers certainly would meet ICH guidelines. And we would look to – and, in fact, we are looking to leverage that safety database, that rich safety database to accelerate or streamline our filings for AXS-12 and AXS-14.

Thanks for the questions. Congrats.

And our final question will come from the line of Joseph Thome with Cowen and Company.

Hi there. Thank you for taking my questions. It's Joe from Cowen. First, on the Alzheimer's data, as you go through what you presented not too long ago, is there anything looking forward to a Phase III that you would change in terms of the enrollment criteria or how long you want to be following these patients in this study? And then, my second question on AXS-12, when looking at the primary endpoints for this study, are you looking at both cataplexy and daytime sleepiness? And maybe is there one that the agency will be looking closer at in terms of regulatory decision? Thank you.

Thank you for the questions. With regards to the next Phase III for our Alzheimer's disease agitation program, we just got the data last week. So, we want to make sure that we continue to mine it to understand it to inform potential design of the next study. With regards to AXS-12, we will be looking at both cataplexy and excessive daytime sleepiness in our Phase III program. Cataplexy is, we believe – all the symptoms in narcolepsy are important, but we believe that cataplexy is one of the ones with the highest unmet medical need. There currently is only one product that is exclusively for cataplexy. And there are a lot of other products that are available for excessive daytime sleepiness. So, we'll be looking at both. And the focus will be on cataplexy.

Great, thank you.

And at this time, there are no further audio questions. Are there any closing remarks?

Well, thank you all for joining us on the call today. We are intensely focused on advancing what we believe to be the most robust late stage CNS pipeline in the industry. We look forward to updating you on our ongoing progress.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.