Good morning, ladies and gentlemen, and welcome to Axsome Therapeutics Second Quarter 2018 Financial Results Conference Call. Currently all participants are in a listen-only mode. Later there will be a question and answer session and instructions will follow at that time. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, 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 financial results press release providing a corporate update and details of the company's financial results for the second quarter ended June 30, 2018 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 these investigational agents, our clinical and non-clinical plans, our plans to present or report additional data, and the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development and possible intend to use of cash and investments. These forward-looking statements are based on current information assumptions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue 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; Nick Pizzie, Chief Financial Officer; and Dr. Cedric O’Gorman, Senior Vice President of Clinical Development and Medical Affairs. Dr. Tabuteau will first provide a pipeline update and a review of upcoming milestones. Following that, Dr. O’Gorman will provide a clinical and scientific update. And then Nick Pizzie will review our financial results. We will then open the line for questions. I shall now turn over the call to Herriot.

Thank you, Marc. Good morning, everyone, and thank you all for joining Axsome Therapeutics second quarter 2018 results conference call. In the second quarter, we advanced our CNS pipeline, and we now look forward to several near term clinical milestones. We remain on track to initiate our planned Phase 3 trial of AXS-07 in acute migraine, and to report results from potentially four clinical trials with AXS-05 over the next two quarters. I will now provide a brief pipeline update and then turn it over to Cedric, who will provide further details. Let us start with AXS-05. Our most advanced CNS product candidate. AXS-05 is a novel oral investigational medicine, which combines glutamatergic, monoaminergic and anti-inflammatory mechanisms of action. AXS-05 is currently in a Phase 3 trial in treatment resistant depression, which we refer to as the STRIDE-1 trial. Enrollment in STRIDE-1 is ongoing. And we anticipate the second final interim analysis, which will be performed to assess efficacy in the fourth quarter of this year. AXS-05 is also in a Phase 2/3 trial in agitation associated with Alzheimer's disease. We refer to this trial as the ADVANCE-1 trial. Enrollment in ADVANCE-1 is ongoing and we anticipate an interim futility analysis for that trial in the fourth quarter of this year. In June, we announced enrollment of the first patient in the ASCEND study, which is a Phase 2 trial of AXS-05 and patients with major depressive disorder or MDD. We anticipate topline results from this trial in the fourth quarter of this year. Finally, as a reminder, in April, we announced enrollment of the first patient in a Phase 2 trial of AXS-05 in smoking cessation. This trial is being conducted under a research collaboration with Duke University. Topline results are now anticipated in the first quarter of 2019.…

Thank you, Cedric. I would now like to turn the call over to our Chief Financial Officer, Nick Pizzie, who will review the company's current financial position.

Thank you, Herriot, and good morning, everyone. I will now cover our second quarter 2018 financial results. Starting with our balance sheet, we had $20.4 million in cash at June 30, 2018 as compared to $26.6 million at March 31, 2018. Turning to the statement of operations, research and development expenses were $5.6 million for the second quarter ended 2018 as compared to $5.0 million for 2017, an increase of $0.6 million. The increase was primarily due to our STRIDE-1 and ADVANCE-1 studies and preclinical work on AXS-05 and AXS-07, which was partially offset by a reduction in the cost of our previously initiated clinical trials and the conduct of preclinical work on AXS-02 and AXS-06. General and administrative expenses were $2.4 million for the second quarter 2018 compared to $1.7 million for 2017, an increase of $0.7 million. The increase was primarily due to higher intellectual property and legal expenses, external fees associated with the operating as a public company as well as an increase in personnel costs. Overall, operating expenses in the second quarter of 2018 increased by $1.2 million to $8.0 million as compared to $6.8 million in 2017. Interest and amortization of debt discount expense was $0.3 million for the second quarter of 2018 and 2017, which was associated with our loan and security agreement with SVB. In sum, the company incurred a net loss of $8.3 million or $0.32 per share for the second quarter of 2018 as compared to a loss of $7.1 million for 2017, or $0.30 per share. We anticipate that our current cash position will be sufficient to fund our anticipated operating cash requirements into the third quarter of 2019. Importantly, we believe that our current financial resources will take us through the next several major clinical milestones, including the next interim analysis and final results of the STRIDE-1 trial for treatment resistant depression, the interim analysis for the ADVANCE-1 trial in agitation associated with Alzheimer's disease, topline results from the ASCEND Phase 2 trial of AXS-05 in major depressive disorder, topline results from the Phase 2 trial in smoking cessation and potentially topline results from our Phase 3 trial of AXS-07 in the treatment of migraine. That concludes our second quarter 2018 financial review. I’ll now turn the call to Mark to lead the Q&A session.

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

[Operator Instructions] Our first question comes from the line of Robert Hazlett from BTIG. Your line is open.

This is Jake Colby on the line for Bert. How do you think about defining success for 05 in the upcoming MDD readout? And what would you need to see the move in the Phase 3 with that program?

As you know, we are now conducting two trials in depression with AXS-05, our Phase 3 trial in treatment resistant depression, and this new Phase 2 trial at MDD. The point of launching the study in MDD was to further elucidate the potential for AXS-05 as an antidepressant. It will allow us to really explore the various properties of the drug that could make it differentiating. For example, in one of the scientific presentations recently, we highlighted the fact that [indiscernible] and does appear to share a similar pharmacology to a fast acting antidepressant ketamine. And so this is -- trial of MDD, for example, might allow us to really look at on sort of action that’s the one thing that we would look at. We are also looking at numerous secondary endpoints. And so, with this trial we really have had the potential to give us a lot of information on the potential of AXS-05.

[Operator Instructions] Our next question comes from the line of Matt Kaplan from Ladenburg Thalmann. Your line is open.

Good morning. Congrats on the progress. Very impressive. Lot of things going on, and readouts throughout your term. You gave great detail on the AXS-05 programs, and want to talk about those as well. But first off just wanted to get some more detail on the start of the migraine Phase 3, and what that could potentially look like in terms of the number of patients and the design of study.

Thanks Matt for the question. So as you correctly pointed out, migraine program with AXS-07 is one of the areas of focus of the company. So we've been focused on making sure that we advance the AXS-05 in two pivotal trials, but also migraine, we believe that this is will be a very significant program for us. AXS-07's profile is potentially very differentiated in the treatment of migraine. So we are on track to initiate that trial this year. So we are targeting the fourth quarter of this year to initiate that Phase 3 trial. In terms of the actual trial design, once we actually launch the study, we will publish a quarter clinical trial that give the exact design of the trial, and we will talk about it in terms of patient numbers. To preview though what the trial design might look like, as you know AXS-07 doesn’t corporate two active agents MoSEIC meloxicam and rizatriptan. And so there would be comparable arms with those individual agents in the trial design. That should not be surprising. And so we are very excited about the potential for AXS-07 for three reasons; one is that we would expect there to be a significant benefit potentially on onset of actions because of a rapid absorption of meloxicam with our MoSEIC technology. We would expect there to be also potentially additive efficacy -- will certainly additive and likely synergistic efficacy between the two active ingredients, one of which rizatriptan is the proven agent in migraine. And lastly, the half-life of meloxicam is long, so it's 20 hours or more. And the reason why that's important is that that could contribute to a reduction in symptom recurrence within a 24-hour period.

That’s very helpful. And then turning back to AXS-05, you're looking at into multiple indications are and depression broadly in agitation Alzheimer's. Can you talk a little about its mechanism of action and kind of the futility of the drug kind of broadly? And any indications like you're looking out in potentially others?

So the -- one of the differentiating aspects of AXS-05 is its pharmacology. It has numerous mechanisms of actions. One way to think about the mechanism of actions of AXS-05 is this to think about it in terms buckets. It does have monoaminergic mechanisms of action, so for example, serotonin reuptake inhibition, norepinephrine Reuptake inhibition, and of course dopamine reuptake inhibition with the bupropion component. And also, I think some of the focus has been though on its glutamatergic mechanisms of action. It is an NMDA receptor antagonist and sigma-1 receptor agonist. And those two mechanisms of actions -- those two glutamatergic mechanisms of actions are thought to underline the opposing and fast acting antidepressant facts of drug like ketamine. In addition to those two mechanisms of action, AXS-05 also has anti-inflammatory properties. Both components have demonstrated anti-inflammatory properties in clinical studies as well as in non-clinical studies. The reason why that mechanism of action is important is that there has been a lot of -- recent research showing that patients, who suffer from depression and, especially treatment resistant depression, do have increased levels of inflammatory cytokines. And inflammation does appear to be a significant part of the pathophysiology of depression, and not just depression but also no inflammation is implicated in other CNS disorders. So that is a mechanism of action of AXS-05 that we have not highlighted a lot in the past, but it's one that we are very aware of and that we think might contribute to the broad applicability of AXS-05 in not only depression, but also in other CNS disorders such as Alzheimer's disease, agitation and numerous other potential limitations, which we highlight and review in our corporate presentation.

Our next question comes from the line of Ram Selvaraju from H.C. Wainwright. Your line is open.

Hi. This is Julian on for Ram. Congrats on all the process. Starting with STRIDE-1, just curious when randomization for that trial is expected to be complete? And for the interim efficacy analysis, how much data is expected to be released? And should we expect to see any P values with that readout?

So for STRIDE-1, the guidance that we have given is we do anticipate to have the results of the second and final interim analysis in the fourth quarter of this year. And as a reminder, that interim analysis is triggered when 60% of the patients not only have been enrolled but without completed the double-blind phase of the trial. And then with regards to full data readout, we expect a full-data readout from STRIDE in the first half of 2019. So I hope that that gives you some sense of enrollment. And with regards to the interim analysis and what is expected from that in terms of P values, it really depends on what the outcome is of the interim analysis for efficacy. There are three potential outcomes. One is that the study stopped for efficacy in which case we would then anticipate, obviously, announcing some topline results, including P values. And one other possibility -- the second possibility that the study stopped for futility, and the third possibility is that the agency recommend that this study continue to full enrollment.

Okay. Got it. Thanks for that. Moving on to ADVANCE-1, it's on the result for the first interim analysis. Is it possible that the perimeters of the trials might be changed such as decision to enroll additional patients?

With regards to the interim analysis for the ADVANCE-1 trial, the purpose of that interim analysis is not refi the study. There are two dimensional outcomes to that interim analysis; one is that the study has allowed to proceed the full enrollment or that the study is stopped for futility.

Okay, got it. And then two quick ones and then I'll just jump back into queue. Are you able to talk about how enrollments going for the ASCEND trial? And assuming positive data from this trial, what would be the next steps for AXS-05 on as a treatment for MDD?

To the ASCEND trial, we initiated that trial in June, enrollment has been going well in that study. And we are on track to report full topline results from that study in the fourth quarter of this year. And with regards to next steps, indication, if the study is positive, then obviously there would be the ability to launch a Phase 3 trial in that indication. One possibility, of course, that we are exploring is potentially combining the efficacy trials in all of our depression programs, TRD as well as MDD.

Okay, great. And my last question then I'll jump back into queue. I was just curious what your thoughts are on the competitive landscape for AXS-07? And has it changed it all since the product candidate was originally formulated?

We think that AXS-07 has the potential to be the [indiscernible] product for the acute treatment of migraine and that is in comparison to products that are currently marketed as well as products that are currently in development. When we embarked on the development of AXS-05, we examined the major reasons for patient dissatisfaction with current migraine products. As a reminder, this is a very large market. There are approximately 40 million Americans who suffer from acute migraine. But it's also very dissatisfied market. So 70%, approximately, of the patients with acute migraine were dissatisfied. And the literature is very clear. Survey after survey patients identify the three major reasons for dissatisfaction being that one -- the drugs weren't going to worked fast enough, which is understandable if you have a migraine. And two, is that secondly major reason for dissatisfaction is that the growth don’t work well enough or consistently enough either the pain relief is incomplete or sometimes the drug works and sometimes it does not work. The third reason, major reason for patient dissatisfaction is that the migraine comes back. And if you look at the pharmacology and the PJ profile of the AXS-07, to date it has potential to address all of those issues. We are starting with rizatriptan, which is a fairly active triptan. And we would expect there to be added efficacy and potentially synergistic efficacy with meloxicam -- with MoSEIC meloxicam, and combined with the not only the rapid absorption of MoSEIC meloxicam, but the long half-life. We would have expected to really address all those issues. So from a competitive perspective, to summarize, we think that the product is very well positioned.

[Operator Instructions] Thank you. That concludes the Q&A session. I will turn the call back to Axsome CEO, Herriot Tabuteau, for concluding remarks.

Thank you all for joining us on the call today. We are committed to finding safe and effective treatments that can make a significant difference for patients suffering from prevalent and disabling CNS disorders. We are pleased with our continued progress so far in 2018. And we anticipate the remainder of the year will be productive, busy and exciting as we focus on achieving our objectives. We look forward to informing you our progress in the months ahead. Thank you again. And operator, you may now disconnect our call.

Thank you, ladies and gentlemen. That does conclude today's conference call. You may all disconnect, and everyone have a great day.