Good morning, ladies and gentlemen and welcome to the Axsome Therapeutics Conference Call. Currently, all participants are in a listen-only mode. [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.

Thank you, operator. Good morning and thank you all for joining us on today’s conference call. Our earnings press release providing a corporate update and details of the company’s financial results for the fourth quarter and full year ended December 31, 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, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development and possible intended 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; Dr. Cedric O’Gorman, Senior Vice President of Clinical Development and Medical Affairs; and Nick Pizzie, Chief Financial Officer. Dr. Tabuteau will first provide a review of significant corporate and clinical developments and upcoming milestones, following that Dr. O’Gorman will provide an update on our ongoing late stage clinical programs and then Mr. 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, Mark. Good morning, everyone and thank you all for joining Axsome Therapeutics fourth quarter and full year 2018 results conference call. Axsome is committed to developing novel medicines for patients with serious CNS disorders, a population that is underserved by the limited treatment options for many of these disorders. We took significant steps toward this goal in 2018 and have continued that momentum so far this year. As a result of efforts by our team, we now have three differentiated CNS product candidates, AXS-05, AXS-07, and AXS-12 in active clinical development across six different indications. Cedric will speak in detail about all of our ongoing clinical trials with these candidates shortly. But first, I wanted to share some of my thoughts on our accomplishments in 2018 and the opening months of 2019. Since this time last year, we have advanced our ongoing clinical trials with AXS-05, our novel, oral NMDA receptor antagonist with multimodal activity. We have unveiled new internally generated product candidates and launched clinical trials in new indications. In 2018, we announced positive outcomes of the interim analysis of STRIDE-1 Phase 3 trials of AXS-05 in treatment resistant depression and the ADVANCE-1 Phase 2/3 trial of AXS-05 in agitation associated with Alzheimer’s disease. Additionally, in little more than 6 months, we initiated, executed and completed a positive ASCEND Phase 2 trial of AXS-05 in major depressive disorder, or MDD. This study allowed us to demonstrate for the first time the rapid substantial and statistically significant antidepressant effect for AXS-05 as compared to an active comparator. Based on these results we now intend to develop AXS-05 for the indication of MDD in addition to treatment resistant depression and plan to meet with the FDA in the second quarter to discuss the potential of regulatory path for the…

Thank you, Cedric and good morning everyone. I will be covering full year 2018 financial results on this call. Starting with our balance sheet, we had approximately $14 million in cash at December 31, 2018, including proceeds from the recently completed at-the-market equity financings and new growth capital term loan, which I will discuss later in greater detail. Our pro forma cash balance was $52.6 million which compares to $34 million at December 31, 2017. Turning to the statement of operations, the company incurred a net loss of $31 million or $1.15 per share for the year ended December 31, 2018 as compared to a loss of $29 million in 2017 or $1.27 per share. Operating expenses in 2018 increased by $5.7 million to $32.8 million as compared with $27.1 million in 2017. Research and development expenses were $23.5 million in 2018 which was $3.5 million above 2017 expenses of $20 million. This increase was primarily attributed to increased costs of our previously initiated clinical trials including STRIDE-1 and ADVANCE-1 initiation and completion of ASCEND study, AXS-07 and AXS-12 study startup and manufacturing costs, offset by a reduction in costs from the CREATE-1 and COAST-1 trials. General and administrative expenses for the year ended December 31, 2018, were $9.4 million as compared to $7.2 million for 2017, an increase of $2.2 million. This increase was driven due to higher legal costs, external fees associated with operating as the public company as well an increase in personnel costs. Interest expense in 2018 was $1.1 million as compared to $1.3 million in 2017, the decrease of $0.2 million was driven by lower interest and amortization of debt discount associated with our loan and security agreement with Silicon Valley Bank. In 2018, we secured our balance sheet through the registered direct offering in October and with received gross proceeds of $8.9 million. To further strengthen our cash position in January of 2019, we have raised $25.8 million in gross proceeds through the sale of shares under our ATM facility with Leerink. This offering fully utilized the ATM facility. In March of 2019, the company entered into a $24 million growth capital term loan facility led by Silicon Valley Bank. The company received $20 million upon closing of the agreement and the remaining $4 million tranche is available to be drawn upon achievement of positive results from our ongoing Phase 2 trial of AXS-12 in narcolepsy. We believe that our current cash position including proceeds from January 2019 equity financings and the March 2019 term loan will be sufficient to fund our anticipated operating cash requirements into at least the fourth quarter of 2021. Importantly, this runway extends beyond the data readouts for all five of our ongoing clinical trials with our CNS product candidates. That concludes our 2018 financial review and I will turn the call back over to Mark to lead the Q&A discussion.

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

Thank you. At this time we will be conducting our question-and-answer session. [Operator Instructions] Your first question comes from the line of Matt Kaplan with Ladenburg Thalmann. Matt, your line is open.

Hi, good morning guys and congrats on the progress this year. I wanted to dig into AXS-12 a little bit, your program in narcolepsy, I guess the question is how can you execute this study as quickly as you have guided for you just recently started it, maybe can you talk about the design of the study a little bit?

Thank you, Matt for the question. I will turn it over to Cedric who will discuss the design of the trial. And with regards to our projections for enrollment, while this is a randomized controlled trial as Cedric will discuss, we are using an approach which is a crossover design and that allows us to utilize really the full complement of patients twice. So in other words while the study we believe is adequately powered to detect the treatment difference because of the smaller number of subjects that should allow us to enroll the study fairly rapidly. And we do have some experience enrolling studies in offering diseases and we are taking those learnings and applying them to this clinical situation. And I will turn it over to Cedric to discuss the trial design. Cedric O’Gorman: Thanks Herriot and hi Matt. We have worked with a lot of experts in the field to identify sites that have experience in recruiting patients who have narcolepsy. So, we really made an effort to find those sites that with having more seamless and access to database of subjects. And then with regard to the study design, it will soon be posted on clinicaltrials.gov but in essence it’s a crossover study for about 20 subjects with narcolepsy will be randomized to receive AXS-12 or placebo followed for 3 weeks and then as Herriot mentioned, the crossover would be such that AXS-12 subjects would go to placebo for further 3 weeks and the placebo subjects will go to AXS-12 for further 3 weeks. The outcomes will be measurements of cataplexy attacks as well as measures of excessive daytime sleepiness and other relative measures in narcolepsy. The crossover would allow one to increase the power to detect a signal in the study.

Okay, that’s very helpful. Thanks for the details. And then just AXS-07, you announced the SPA a short time ago, can you give us some details on the SPA with the FDA for this Phase 3 study and what’s included in it?

So, with regards to the SPA, it’s an agreement with the FDA on the overall design of the study, including specifically the inclusion and exclusion criteria in the trial as well as the endpoints in the study, so the primary endpoint of the study and then importantly the statistical analysis of the trial. And now the point of the SPAs is that if the study is successful, then the study would count as a registration trial. So really it’s a trial design, including inclusion and exclusion criteria endpoints and also importantly statistical analysis.

And in terms of being able to file for approval on a single study, is that included in the SPA?

That is not specifically included in the SPA. However, during the SPA process that is something that we explored and based upon the feedback from the agency during the SPA process, we do believe that only one Phase 3 trial maybe needed in order to file an NDA.

Thank you. And then just a couple of more questions in terms of the Alzheimer’s agitation study, can you talk about how enrollment is progressing there and what your thoughts are in terms of who you are in the progress of that study?

Sure. I will turn that over to Cedric. Cedric O’Gorman: Yes, very pleased with progression of this study, where approximately 40% is the target number of subjects to be enrolled. We are on track for the guidance that we have given for top line data in the first half of 2020.

And last question you mentioned some in your prepared remarks about the Axsome PPC subsidiary, can you talk about kind of business development opportunities that, that presents for the company and how you are thinking about PPC? Cedric O’Gorman: You are correct that Axsome PPC does present the way we see it business development opportunities. It certainly is an important asset for the company and for Axsome shareholders. And that it does include three product candidates and one of which is in Phase 3 trials and also it includes some pretty large indications, so not only pain, but also osteoporosis. So, the reason why we place those assets into Axsome PPC was to increase their visibility with regards to business development opportunities. And so we view these assets as potential source of monetization, which could help fuel the reservoir pipeline, but certainly to generate returns for shareholders.

Thanks for taking the questions guys. I will jump back in the queue.

Your next question comes from the line of Bert Hazlett with BTIG. Bert, your line is open.

Thanks. One or two on 05 and then one on 07, congrats on the progress in 08 and beyond. So with the bolstered cash – I guess typically run the trial in series you have done one Phase 3 and then looked to another Phase 2 and looked to another with bolster substantial position, is there a chance in MDD for instance that you might be running two Phase 3s in parallel moving for other indications or perhaps for smoking cessation moving forward?

Thank you, Bert for the question. So we definitely do have a bolstered cash position which puts us in a very comfortable situation and allows us to complete all of our ongoing clinical trials and well beyond that. It certainly does provide us with added financial flexibility. Right now, our plans are as we have laid out which is to complete our ongoing clinical trials. We have numerous data read outs coming up over the next several quarters. And it remains to be seen if there is opportunity for additional investment and but right now our plans are as we have laid them out.

Okay. Thank you. So then just getting to the specifics of TRD assuming success in STRIDE-1 in the second quarter, is it your intention, is the – as you can best project it now to simply mirror STRIDE-1 in another Phase 3 study and move forward in that indication or are there other possibilities assuming success in that trial?

Assuming success in STRIDE if we do need another trial in treatment resistant depression we would certainly at least try and replicate whatever elements of the STRIDE-1 trial that led to success. We are – as we indicated in our prepared remarks, we do anticipate meeting with the FDA in the second quarter of this year in order to discuss in light of the positive results that we have with the ASCEND Phase 2 trial in MDD in order to discuss the potential regulatory path for a broader MDD indication. So once we meet with the FDA we would then anticipate updating you.

Okay. Thanks for that. And then just one quick one on AXS-07, how are meloxicam or rizatriptan arms treated in the trials, statistically do you have to separate it from those or is it just separation form placebo that’s going to be important here, just a little bit of more color on that trial and the statistics involved? Thank you.

So just a brief background on the MOMENTUM trial of AXS-07 for the acute treatment of migraine, it does include meloxicam arm or rizatriptan arm and the placebo arm, so it’s a four arm trial. And clearly we are looking for a separation between AXS-07 and placebo. But because of the two components of AXS-07 we do have to show superiority over the individual components. So we would have to show superiority over the rizatriptan arm as well over the meloxicam arm.

Your next question comes from the line of Charles Duncan with Cantor. Charles, your line is open.

Good morning guys. Thanks for taking my questions. Had a couple on 05 and one on 07 as well. On 05 first of all, if you can just remind us on the TRD study, what are the some of the key elements that you have designed into this study that may enhance the probabilities of the success, TRD is a tough indication to treat and I am wondering what you think are the key elements of patient enrollment criteria or whatever design that may result in that trial being a success?

Good morning, Charles and thanks for question. I will turn it over to Cedric. Cedric O’Gorman: Yes. Hi, Charlie. Thanks for the question. So as you know, close to 40%, if not more patients are deemed to be treatment resistant in terms of the major depressed disorder and that’s commonly recognized definition of that in having failed two or more anti-depressants of adequate dose duration in their depressive episode. So we have been very careful in STRIDE-1 study to be able to categorize these patients as truly treatment resistant. So, when they are coming into the study, there needs to be very, very good medical clinical documentation that they have failed one or two antidepressants of adequate dose and duration in their depressive episode. Now, then we have a initial stage of this study for patients who are depressed are treated for 6 weeks with bupropion and it is only after those 6 weeks that patients who have failed to respond to bupropion are randomized with purposes of the comparison of AXS-05 versus continuation of bupropion as the control and the importance of this is the prospective leading is that it allows us now to prospectively identify patients who are failing an adequate dose of an antidepressant for an adequate duration of time. So this gives us even further confidence, these patients are truly depressed – sorry truly treatment resistant. So, the end of that open-label, either patients now who have failed two or more antidepressants remain depressed and at that point they are randomized. So, it’s a nice way to really ensure that you have the correct population in the study. And then an average total score is used as primary outcome measure which was also the primary outcome measure used in the recently successful ASCEND Phase 2 study that was in the broader major depressive episode. And then we make sure that we use clinical sites who are trained and familiar and experienced in rating these kind of studies in patients. So I hope that comes close to answering your question.

Yes. And if I may just add one other element to Cedric’s answer is that we also implement in addition to all of the elements that Cedric just mentioned, we also do implement quality control measures in our study to make sure that appropriate patients are enrolled. So in other words not just patients who have the appropriate diagnosis and that is absolutely critical, but also patients who are appropriate to be enrolled into trials. So we have not disclosed what those specific measure are, but it is something that we are keenly aware of and that we are taking and we have taken steps to make sure that the quality of the study is as high as possible.

Okay, that makes a lot of sense to me and I appreciate all the color, Cedric. And then you Herriot provided, it sounds like there has been an ongoing auditing of the sites and the types of patients that have been enrolled in that trial?

Yes.

Okay. And moving on second question on O5 with regard to Alzheimer’s agitation, I am just kind of wondering and this may seem like almost silly question, but it is not meant to be, how do you define an Alzheimer’s patient, is it defined – is that patient defined clinically or through imaging or both?

Yes, thanks, Charles. So there is a standard approach whereby the patient is clinically deemed to have a diagnosis of probable Alzheimer’s disease. As you know, the absolute definitive diagnosis of pathology of Alzheimer’s disease can only happen at postmortem, but the approach to these types of trials when it comes to Alzheimer’s disease is a cognitive assessment, which prior clinicians have deemed to be such that this patient has a diagnosis of probable Alzheimer’s disease.

Okay, that’s helpful. And then moving on to 07, when you think about that target product profile and consider the rapidly evolving migraine treatment landscape, I guess, what do you think is the key elements of or features of that product profile that you see is serving an unmet need, what is the unmet need and why do you think that this product in particular is well suited for that?

So, thank you for the question. We’re pretty excited – we’re really excited about AXS-07. And the reason for that is, we do think that the product profile is very differentiated. And that point of differentiation is efficacy. So, in almost all patient surveys, what patients report as the major reason for dissatisfaction is efficacy and so with AXS-07, we put together one with our MoSEIC technology a way to rapidly deliver meloxicam. And so that should help significantly with onset of action and then we’ve found that with also triptan, which is considered to be fast acting. So, we – so with the multiple mechanisms of action, we do expect not only a rapid onset of action, but also superior and consistent efficacy. So, that remains to be seen of course in the results of our clinical trials, but that was the way that, that we design the product candidate. So, it’s really efficacy. Now, another aspect of efficacy is not just the rapid onset of action. It’s not just the strong and consistent efficacy, but it’s also symptom recurrence or lack of symptom recurrence. So, one of the three reasons for patient dissatisfaction is also that the pain comes back. So, with AXS-07, which includes MoSEIC meloxicam, what we’ve shown is that not only do we get a really rapid absorption of MoSEIC meloxicam, but there is a roughly 20 plus hour half-life to the meloxicam, which means that the drug stays around and we think that, that should help reduce symptom recurrence. Now when you put all that together then that should result in not only in terms of – not only in terms of patient benefit, but they should also result in pharmacoeconomic benefits. In terms of the evolving migraine landscape, what’s nice about AXS-07 is, we are targeting 100% of the migraine population. And as you know there are close to 40 million migraineurs in the U.S. and AXS-07 is designed for the acute treatment of migraine. So, 90% of that population are patients, who have episodic migraine and the other 10% have chronic migraine and those patients are the candidates for preventative treatment and even the patients will receive operative treatment, they do eventually have migraines and once they do, then they do – they will require an acute treatment and that’s where AXS-07 will also fit into that segment of the population.

It’s helpful, Herriot. One follow-up question to that would be that given the mechanism of action at least with regard to the riza component, rizatriptan component. I’m wondering what percentage of the 40 million migraineurs you mentioned you believe have contraindications for triptan use because they have known or suspected cardiovascular risk? And I’m wondering if you think the rapid onset is going to be a liability or just a non-issue for 07 in that particular part of the patient population?

Well, I think – we think rapid onset of action in migraine is always a benefit. Patients want the migraine pain to be gone as quickly as possible. Anyone who’s experienced the migraine would attest to that. In terms of the percentage of patients, who may have contraindications to triptans, the – I think that I will refer you to actually a survey, which you conducted I believe recently, which did show I believe that and maybe you can speak to that, but I do believe that the neurologists in the survey, the doctors in the survey indicated that only about 10% to 20% of their patients were contraindicated. So, the vast majority of patients actually would be available for AXS-07.

Appreciate that callouts and you are right, that’s always what we have modelled in terms of the opportunity for mechanisms beyond triptans related to the cardiovascular risk. So, appreciate that color and callouts. Thanks.

Thank you.

[Operator Instructions] Your next question comes from the line of Ram Selvaraju from H.C. Wainwright. Ram, your line is open.

Hi, thanks very much for taking my questions. There are three quick ones here. I was wondering if you could comment on the expected efficacy profile of AXS-12 in narcolepsy and how that is likely to compare to existing approved drugs in the space? Obviously, we’ve realized that the majority of those – I think all of those drugs that are currently approved for this indication are scheduled and reboxetine would have the potential to be the first non-scheduled agent, but wanted to see if you could comment on its efficacy profile as expected based on the pilot study with respect to both symptoms of EDS, as well as cataplexy? Secondly, I was wondering if you could say a few words about the IP portfolio specifically on neridronic acid and whether you have seen any new developments in potential opportunities to monetize that? And thirdly, I was wondering if you could just walk us through on a granular level since the pipeline is rapidly maturing and there’s going to be multiple additional clinical programs being launched over the course of the remainder of this year, what specific trial programs are factored into and/or covered by your existing cash resources? Thank you.

Thank you, Ram, for the multi-part question. So, with regards to AXS-12 and the efficacy profile, so what we like about AXS-12 is this – is that we think that it may be able to address two of the key symptoms of narcolepsy, those being cataplexy and excessive daytime sleepiness. As a reminder, there are only five products that are currently approved to treat the symptoms of narcolepsy, and of those only one product is approved to treat cataplexy associated with narcolepsy. So – and that product is sodium oxybate, which is effective for many patients, but which is as you know does have some limitations including the fact that it is scheduled. So, we’re really looking forward to the results of the CONCERT trial with AXS-12 to see its potential impact on cataplexy. And as Cedric mentioned, we will also be measuring and assessing excessive daytime sleepiness. With regards to the IP portfolio and specifically as it relates to neridronic acid, as a reminder, neridronic acid is a bisphosphonate compound, which is being developed by a third-party for the treatment of complex regional pain syndrome. It is currently based on public disclosures in two large Phase 3 trials and has received also breakthrough therapy designation from the FDA. We do have more than 20 issued patents, which cover the use of neridronic acid for the treatment of complex regional pain syndrome. And we have also lately been getting new patents which cover neridronic acid for the treatment of complex regional pain syndrome. So that patent portfolio does continue to grow. And so in terms of the opportunities for monetization, we do believe that this is clearly an asset given our strong patent position with regards to neridronic acid and also the potential of the product in the treatment of complex regional pain syndrome. And your third question was with regards to the trials and programs, which are covered or included in our guidance in term of cash runway. So as a reminder, our guidance for cash runway is into the fourth quarter of 2021. And I’ll turn it over to Nick, who will comment on what is included in that guidance.

Sure. Thanks, Herriot. Yes, so basically everything that we’ve announced already – all our announced studies are fully funded with our current cash resources. So that does include the STRIDE-1 and smoking cessation that’s expected to be wrapped up in Q2 along with AXS-07 for migraine, and, obviously, narcolepsy, and also the ADVANCE-1 trial, which is the first half of 2020.

Great. Thanks very much. And then one quick follow up, you guys may be aware of efforts to position dexmedetomidine in the treatment of various manifestations of agitation. And I was wondering if you could comment on whether you view that as potentially complementary to your own ongoing efforts in the agitation space particularly within the context of Alzheimer’s related agitation or if you see it as competitors? Thank you.

So, we’re always happy to see other companies try to develop products to treat some of these CNS disorders especially Alzheimer’s disease agitation. Since as you know there’s currently nothing approved to treat Alzheimer’s disease agitation. It is very distressing and it affects a large patient population. So, we really applaud the fact that others see the clinical need as we do. And it remains to be seen, of course, what the clinical results are of the trials with the other agents. We’re really excited about our approach because we do think that they’re strong proof-of-concept. We think that we’re running a quality trial and we’ll know soon enough what the clinical profile is exactly in Alzheimer’s disease agitation.

Great. Thanks very much, and congratulations on all the progress.

There are no more questions. I will turn the call back over to Axsome’s CEO for any concluding remarks.

We are very pleased with the progress that we’ve made in 2018 and thus far in 2019. If our products are successfully developed, these candidates have the potential to make meaningful positive changes in the lives of patients living with CNS disorders. We are committed to advancing our portfolio of differentiated investigational CNS medicines over the remainder of this year. And we look forward to multiple top-line data read-outs from our ongoing clinical trials starting in the second quarter. Thank you again for joining our call.

This concludes today’s conference call. We would like to thank you for your participation. You may now disconnect.