Axsome Therapeutics, Inc. (AXSM) Q4 2021 Earnings Report, Transcript and Summary

00:07 Good morning, and welcome to today’s Axsome Fourth Quarter and Full-Year 2021 Financial Results. My name is [Candice] [ph] and I will be your moderator for today’s call. [Operator Instructions] 00:33 I would now like to pass the conference call over to our host Mark Jacobson, Chief Operating Officer. Mark, please.

00:46 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 of 2021 crossed the wire a short time ago and is available on our website at axsome.com. 01:06 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 investinational 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 plans; commercial plans and possible intended use of cash and investments. 01:37 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. 01:53 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. 02:12 Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Lori Englebert, Senior Vice President of Commercial and Business Development; and Dr. Amanda Jones, Senior Vice President of Clinical Development. 02:28 Herriot will first provide an overview of the company and then review recent developments and upcoming milestones. Following Herriot, Lori will provide a commercial update, and then Nick will review our financial results. We will then open the line for questions. Questions will be taken in the order they are received. 02:46 And with that, I will turn the call over to Harriot.

02:51 Thank you, Mark. Good morning, everyone and thank you all for joining Axsome Therapeutics' fourth quarter and year-end 2021 financial results and business update conference call. 2021 was the year of continued progress which has put us in a position to potentially launch two new investigational medicines for patients living with depression and migraine. 03:14 I will provide an update on our development pipeline before turning it to Lori, who will provide a commercial update. Starting with our first lead product candidate AXS-05, which is undergoing an NDA review for the treatment of major depressive disorder. The FDA previously informed us of two deficiencies related to analytical methods in the Chemistry, Manufacturing, and Controls section of the NDA. 03:41 We submitted a response addressing these deficiencies. The FDA has acknowledged receipt of the response and to date, we have not been made aware of any other deficiencies related to the NDA by the FDA. AXS-05 is also being developed for the treatment of Alzheimer’s Disease Agitation. Enrollment in the Phase 3 ACCORD trial for this indication is progressing. 04:09 Currently, blinded relapse events are below projections. This may imply a potentially greater than projected overall durability of effect in the study, which would have implications for the duration of the trial. In light of these observations, we are evaluating the design of the study and will provide an update following consultation with the FDA. With regards to the development of AXS-05 in smoking cessation, we intend to provide timing on initiation of that trial in the coming months. 04:43 Moving on to our second lead product candidate, AXS-07, a multi-mechanistic acute treatment for migraine. The NDA for AXS-07 was accepted for review by the FDA with a PDUFA target action date of April 30, 2022. The FDA previously notified us that due to COVID-related travel restrictions, they might be unable to complete a required inspection of a contract manufacturing facility prior to the PDUFA date. 05:13 We have since been informed by the FDA that it does not anticipate any issues with completing the facility inspection prior to PDUFA. With the NDAs for AXS-05 and AXS-07 under active review, Axsome launch preparations are underway, and Lori will provide details on our commercial launch readiness. 05:36 The rest of our rich pipeline continues to advance. For AXS-12, our product candidate being developed for the treatment of narcolepsy, enrollment in the SYMPHONY Phase III trial is progressing and top-line results are anticipated in the first half of 2023. 05:54 For AXS-14, our product candidate for the treatment of fibromyalgia, manufacturing and other activities related to the planned submission of an NDA are ongoing, and we expect to submit the NDA for this product candidate in 2023. 06:11 I will now turn the call over to Lori, who will provide a commercial update.

06:17 Thank you, Herriot, and good morning, everyone. 2021 was a year of intense commercial preparation, and I'd like to take a moment to express my sincere appreciation to the team for their continued passion, commitment, and excitement associated with potentially bringing two new therapies to patients. I am extremely proud of the launch preparation efforts achieved over the past year. 06:41 The opportunity to provide new therapeutic options for patients affected by depression remains substantial. Recently, the Lancet published an article by the Lancet World Psychiatric Association Commission, deeming depression, a global health crisis. 06:59 The poignant and powerful article calls for immediate and united action to reduce the global burden of depression, stating that the world is failing to tackle the persisting and increasingly serious global crisis of depression. That article is one of many data points, demonstrating an undeniable urgent need to help address this burden and bring support to those affected by the disease. 07:24 Our approach to commercialization for AXS-05 is innovative and purposeful, and we are prepared to execute if approved. Field leadership remains excited and have fully recruited the field force, all of whom are ready to join Axsome immediately upon approval. 07:41 The market access team continues to engage in permitted payer discussions, in sharing awareness of Axsome, and the product profile. Distribution and patient support services are ready to turn on at launch and marketing materials are ready to be deployed, pending adjustments for final label. 08:00 If approved, AXS-05 would be an important new treatment option for the many Americans living with depression, and we are prepared and ready to bring this meaningful innovation to patients. 08:13 I will now shift gears to address launch preparations for AXS-07 for the acute treatment of migraine. Despite recent innovation, there continues to be close to 70% dissatisfaction rate with currently available therapies, demonstrating high unmet need for the 37 million Americans who experience migraine. 08:31 Given the current migraine landscape, our commercialization strategy for the acute migraine market will be strategic and highly targeted. In terms of preparation, marketing efforts and launch planning are well underway and tracking accordingly. 08:46 Permitted payer discussions have commenced and sales force recruiting is underway. Consistent with the AXS-05 sales rep offers, all offers for the AXS-07 salesforce will be made contingent upon approval. We are excited about the opportunity to potentially bring to market another option for the many Americans suffering from migraine. 09:10 Lastly, our Digital Centric Commercialization or DCC platform remains fundamental to the commercialization strategy. The DCC platform is a technology-enabled platform, designed to use streamlined systems and digital enablement tools, combined with sophisticated data and analytics to allow for a more effective, efficient, and meaningful engagement with physicians and patients. 09:35 The platform is fully implemented, tested, and ready for execution. Our commercial launch strategy is innovative and purposeful with the intent to bring important new products to market in a meaningful way. 09:49 The differentiated clinical profiles for both AXS-05 and AXS-07 have the potential to bring significant benefit to patients and physicians who treatment them. We remain excited about the opportunity to potentially bring these important new products to market. 10:05 I will now turn it over to Nick who will review our financials.

10:09 Thank you, Lori, and good morning, everyone. Today, I will discuss our fourth quarter and full-year 2021 results and provide some financial guidance. We ended the year with approximately $87 million in cash, compared to roughly $115 million at the end of the third quarter, a net decrease of approximately $28 million. 10:27 Inclusive of utilization of our ATM facility in Q1 2022, our proforma cash balance as of year-end is approximately $106 million. R&D expenses were $13.8 million for the quarter ending December 31, 2021 versus $17.4 million for the comparable period in 2020. The decrease was due to the conclusion of several clinical trials, which were ongoing in the comparable prior period. 10:55 For the year, R&D expenses were $58.1 million, compared to $70.2 million for fiscal year 2020. R&D expense during 2020 included a one-time charge of $10.2 million related to the Pfizer license agreement. 11:12 G&A expenses were $18.8 million for the quarter ending December 31, 2021 and $10.4 million for the comparable period in 2020. The increase was primarily related to pre-commercial activities at personnel expense along with an increase in non-cash stock compensation expense. 11:32 For the year, G&A expenses were $66.6 million, compared to $28.9 million for the comparable period in 2020. The increase was primarily due to the build-out of the commercial function along with an increase in stock compensation expense. 11:48 Net loss was $34 million or $0.90 per share for the three months ended December 31, 2021, compared to a net loss of $29.2 million or $0.78 per share for the comparable period in 2020. 12:02 Net loss for the year was $130.4 million or $3.47 compared to a net loss of $102.9 million or $2.77 per share for fiscal year 2020. As a reminder, in Q4 of 2021, we expanded our term loan facility with Hercules Capital to $300 million with up to $120 million available upon FDA approval of AXS-05 in MDD and AXS-07 in migraine and access to an additional $130 million thereafter. This committed non-dilutive capital gives us additional financial flexibility through both anticipated potential commercial launches for AXS-05 and AXS-07. 12:51 We believe our year-end proforma cash position of $106 million along with the remaining committed capital from our $300 million term loan facility, is sufficient to fund our anticipated operations, based on our current operating plan into 2024. 13:08 That concludes our fourth quarter and full-year 2021 financial review. I will now turn the call back to Mark to lead the Q&A discussion.

13:17 Thank you, Nick. Operator, may we please our have our first question.

13:26 Thank you. [Operator Instructions] Our first question comes from the line of Charles Duncan of Cantor Fitzgerald. Your line is now open. Please go ahead.

14:01 Hi. This is Pete Stavropoulos on for Charles. Good morning and congratulations on all the progress. First question is for 005, can you provide any color on the next steps with the FDA and anticipated timing? And has there been any other dialogue with the FDA relating to anything about efficacy or safety or anything else?

14:25 Great. Thank you for the question. So, I'll turn it to Mark to talk about the regulatory communications and interactions with the FDA.

14:34 Good morning. So, the current snapshot is as you're aware, we were made of two deficiencies pertaining to CMC in particular analytical methods, a number of months ago. We subsequently responded to those efficiencies addressing them and FDA has confirmed receipt of those acknowledgement receipt and has told us they are reviewing our responses. 15:00 So that's still the current snapshot. We have not been made aware of any other deficiencies or anything like that. No discussion around efficacy, safety, or things like that. And as that proceeds, we'll continue to keep you updated. In terms of how we're thinking about timing, we don't have any guidance for you or specific feedback that we’ve received. So, what we're doing for planning purposes is, we're using kind of the major amendment framework to inform our planning processes. And just as a reminder to that, during the course of a normal review, if there is a major amendment submitted that FDA accepts to review that typically extends the PDUFA clock by three months, in total. 15:48 And so, again that's our guidance. We haven't been told by FDA that that's the process or procedures they're using, but that's what we're using just for planning purposes. So, hopefully that’s helpful.

16:01 Yeah. Thank you. And for 05 in Alzheimer's agitation, can you give us a sense of how enrollment is going and has there been any impact by COVID?

16:14 Sure. Thanks for the question. Enrollment is proceeding well and it puts us on track to meet our guidance of the first half of 2023 in terms of reporting results. We did discuss in the release this morning that the target number of events, which determines actually when we would be able to stop the study that is – it's a good thing that those events are lower than our projections because it implies potentially greater than expected durability of effect, but it does make us want to look at the design of the trial and also take advantage of the fact that we have Breakthrough Therapy designation with the FDA for the syndication and consult with them. 17:11 We're very excited that this is pioneering work, which we are conducting and this is the first time that this study design has been used in the syndication in Alzheimer's disease agitation with AXS-05. And so, we want to make sure that we're looking at the study very carefully.

17:32 Alright. And switching gears and last question for 07, given the treatment landscape for migraine with oral CGRP drugs and taking share from the triptan’s as well as the CGRP monoclonals, can you help us understand the residual unmet need and product positioning?

17:56 Yeah, Hi. I’m happy to take that. Thanks for the question. So, the migraine landscape continues to have a high unmet need. Recently, as recently as a year ago, Champ, a well-known patient advocacy organization performed a very extensive survey, which shows that 70% of patients are still dissatisfied with the current therapies available. 18:18 And to give you a further data point that I think was fairly – pointing and driving that point home is that that survey revealed that 55% of migraine patients have cycled through at least 10 different therapies. It's a point that that isn't lost on me that cycling through that many therapies means that there's for sure a continued high-level dissatisfaction. 18:43 And again, that was as recently as a year ago. And I also just want to make, mentioned that triptan’s are still 85% of the market share, out in the current treatment landscape. We do think that given our clinical profile, there's a great potential for the product.

19:04 Alright. Thank you for taking our questions.

19:10 Thank you. Our next question comes from Joon Lee of Truist Securities.

19:18 Hey, guys. Thanks for taking our questions and thanks for the updates. So, just to summarize your response to the prior question, you're working assumption based on what you call a major amendment framework is a three month extension under PDUFA, is that correct? And can you share any references supporting that assumption?

19:39 Hey, Joon, it's Mark. So, don't take that as written in stone, we're just using that for something to allow us to run the business and for planning purposes. And why do we think about it like that? Because again during the course of a normal review, if you have a substantive addition amendment or additional data analysis, etcetera that FDA accepts to review, right, if they accept to review it that's a major amendment. And then depending on what you submit, the clock can be extended by, say, 2 months to 3 months depending on the nature of the content. 20:17 So, if you go on to the FDA's website and check out their guidance, the desk reference manual and things like that, it gives you categories of what triggered, say a 2-month or a 3-month, and we’re just assuming for planning purposes given the timeline extension at play given that there's no PDUFA clock, we're assuming that that 3-months is, why the 3-months because that's typically the time that FDA has determined they need in order to review additional data. 20:47 So, it's similar here, but we're just off the clock. And so, that's the thinking of it. And is it going to be 3-months, we don't know. We haven't – again, we haven't received that specific feedback that they're going to take action in 3-months from our submission. That's not what it is, but we think it's in absence of any direct commentary like that, that's what we're using because that's information that FDA has provided publicly in terms of the normal course of a review. 21:17 So, no other references for you besides standard FDA processes and procedures.

21:25 Understood That's fair. And thank you so much. That's helpful. And then one more question. Regards to your ACCORD study in Alzheimer's agitation, you're seeing a lower event of relapse than you projected. And then you're implying that that could be due to drugs having a greater than anticipated effect. And then you're looking to have a dialogue with FDA for potential trial amendments, what kind of amendment did you have in mind? Is this an interim look and an interim analysis so that for possibility of a superiority at interim? We love to hear your elaboration on what you hope to accomplish with that meeting with the FDA on ACCORD? Thank you.

22:07 Yeah. So, Joon, thanks for the question. So, the reason why we mentioned that is, when you conduct and design a randomized growth study, the timing of when you stop that study is kind of [up in the air] [ph]. It depends on the number of events as opposed to standard parallel group design where the study might be, let's say 5-weeks or 6-weeks in duration. And so, we do watch the event rate carefully. 22:42 And also, typically the way that those parameters are set out prospectively is that it's based on prior information with a particular indication in the case of Alzheimer's disease agitation, there currently is no product that is approved. 23:01 And so, there's very little in terms of precedent. So, we want to make sure that given that the study is blinded and we actually don't know what's going on, I want to make sure that we look at the design very carefully and that we dialogue with the FDA to make sure that this is an appropriate study design.

23:27 When can we expect an update on that? Thank you.

23:34 This is something that we would expect to provide to the Street fairly quickly. So, this is active, as you know, the study is ongoing and we do have an open dialogue with the FDA on the indication.

23:49 Great. Thank you.

23:52 Thank you.

23:56 Thank you. Our next question comes from Vamil Divan of Mizuho Securities. Your line is now open. Please go ahead.

24:12 Okay. Thanks for taking the questions and for the update. So, one thing just to clarify because we get this question a lot [Technical Difficulty] on ongoing and the events are not accruing the way initially expected. So, just to be clear, so you don't know, given no sense of whether it's fewer events in the treatment arm or potentially pure events in the placebo arm or both, just to be clear, right, obviously if it's pure events in [indiscernible] that's good. But at this point, we just don't know. So, if you can just clarify that because we're getting a couple of questions I want make sure that's clear. 24:43 And then my second question going back to the 05 discussion on MDD, I think it's just been confusing, I think for you and for all of us, on that sort of stake with the FDA where you did not receive sort of an official CRL, but there’s been back and forth dialogue. So, I’m just wondering if you’ve received any other further insights from the FDA, so why does the unusual path taking place is there? why wasn't there some more formal communication and actual announcement and then maybe official push-out of the action. It should probably be helpful for your planning purposes, as well as I'm just curious if you have any other insights on why it’s gone this route as opposed to what we've seen previously? Thank you.

25:27 Sure. Sure. I'll let Amanda answer the first question and then we'll address the second question.

25:33 Sure. So thanks for the question. So, the relapse rate that we're looking at, it's blinded. So, this study that study period is fully blinded. So, we don't know which treatment arm that relapses are recurring in. So, that's…

25:51 And then with regards to the further insights into why the FDA delay? We don't really know, what we do know that has been publicly discussed is, which also is reflective of what's been happening with other PDUFA gold in general in the industries is, there is a capacity, a resource constraint at the FDA. Could that be contributing to this particular situation? Perhaps what we are focused on is making sure that we respond to the FDA as quickly as possible, in the best possible fashion to allow them to continue the review of the NDA. 26:37 So, we're happy that they have continued to review the NDA. And with regards to the CMC deficiencies that were – the FDA was very prescriptive in terms of what they wanted to see and our team was able to respond to that. So, we'll continue to do that. Currently, there are no open items as Mark mentioned.

27:07 Okay. Thank you.

27:13 Thank you. Our next question comes from Marc Goodman of SVB Leerink. Your line is now open. Please go ahead.

27:26 Yes. Good morning, everyone. Can you talk about just on those, I got a couple of questions. I know 07, first of all, has the FDA done the manufacturing inspection yet, have they told you that if there's a date, if they haven't done it yet?

27:44 So, with regards to 07, what they have told us is that completing the inspection by the PDUFA date will not be an issue.

27:55 Right. But have they done it yet?

28:01 Yes. So, in the typical course of an NDA review, we made an exception with AXS-05 during the unusual situation. We refrain from providing the back and forth, but we have disclosed, the FDA has told us directly that their prior warning that there might be a delay in the PDUFA date because of a delay in conducting the facility inspection, if that is no longer an issue.

28:33 Have you started labeling discussions on that product yet?

28:39 So, again, we won't be commenting on the back and forth. However, the PDUFA date is still valid, which is April 30 and typically, labeling discussion is just to give you a sense of timing of a rhythm of NDA reviews, typically, those occur at approximately one-month prior to the PDUFA date.

29:10 Well, then maybe you can just flip to 05, and when did you file your response exactly to FDA, so we can know when that 3-months in your head, you know the clock started in your head?

29:28 Hey Marc, it’s Mark. And so that was around year-end, the first part of the year, what we're tethering to is, when we received acknowledgment of receipt and confirmation of review, and that's around the time we 8-K’d that, which I think was like mid-January. And that's how we're thinking about, I guess you could say like potential [Multiple Speakers] for potential range, I think somewhere in there, if you add three months, but again that's not guidance from us, that's just potential range where something could occur.

30:19 Right. So, has there been any type of label and negotiations on this product, or will you not comment on that either?

30:31 So, Marc for AXS-05, given the unusual situation, we have sought to provide the street with updates that are definitive. So, whenever we get anything definitive from the FDA, we have provided an update given the unusual situation, the unusual situation being lack of a PDUFA date, but with an ongoing review. So, we do think that that would be something that is definitive, and so currently you could expect that once we have something definitive on that front, that we would look to let the street know.

31:11 And something definitive would also be, if you responded and the FDA basically came back and asked you a follow-up question, would that be definitive? Like, has that happened yet? They acknowledged your receipt, but have they actually asked you for anything else or any [indiscernible]?

31:31 Yes. So, what we said is that we would let the Street know once there is anything definitive and that's clear from the FDA. We've been doing that. And so, if you have not heard anything then there is nothing.

31:49 Right. Okay. And then just completely different subject that the smoking cessation, can you just describe the type of study that you're planning in the program that you're planning?

32:01 Yeah. So, I'll turn that over to Amanda.

32:04 Sure. So, consistent with our prior practice, we'll reveal the whole study design once we announce the launch of it, but just to speak generally, the study design will be similar to other registration trials for smoking cessation products, these designs typically incorporate short treatment periods followed by treatment free observation period.

32:31 And this is going to start when?

32:36 We intend to provide further guidance on initiation of the study within year.

32:43 Okay. Thanks.

32:48 Thank you. Our next question comes from Joseph Thome from Cowen and Company. Your line is now open. Please, go ahead.

33:01 Hi there, good morning and thank you for taking my questions. Maybe for the AXS-05 review, I know you highlighted at the top line merit data to the FDA middle of last year, have you provided any additional data to the agency on that trial? And that's my first question and I have a would follow-up.

33:25 So, we did make the FDA aware of the results of the study and provided that information to the FDA. And we have not made – we have not provided any additional information apart from the results of the trial.

33:45 Okay. And then on the AXS-07 review, are the analytical concerns that popped up with AXS-05 applicable to AXS-07, did you have to make any changes there or is that specific to AXS-05?

34:03 That was specific to AXS-05. So, we don't see any direct connection between the two.

34:16 Okay. Perfect. And then maybe just last one on Alzheimer’s agitation update, I guess how consistent are agitation symptoms between patients? Are we now hitting where it's just been too long for too many patients or is it common that you're going to have patients that have most of your disease and maybe just wouldn't have had an agitation relapse without treatment, kind of how consistent is the [thesis here] [ph]?

34:45 There definitely is variability in the symptoms of the disease. So, patients who have Alzheimer's disease who are agitated, they have they have a range of symptoms. So, for example, one of the common symptom scale, the Cohen-Mansfield Agitation Inventory has 29 items. So, and each of those items corresponds to a separate behavior. And those behaviors cluster into different groups. And so that reflects the variability in the presentation. So, agitation can be manifested in different ways depending on the patient.

35:34 Okay. Thank you.

35:41 Thank you. Our next question comes from the line of Matt Kaplan of Ladenburg Thalmann. Your line is open. Please go ahead.

35:54 Hi. Good morning. I just wanted to shift topics a little bit, as maybe for Lori, can you talk a little bit about your commercial prep and specifically how you interactions have been going with payers and discussions for 05 and 07 on the payer front?

36:16 Yeah, Hi Matt. Thanks for the questions. So, as I’ve stated in the prepared remarks, commercial prep for 05 is, we are ready to go and 07 is well on its way tracking accordingly to potential launch plans. 36:33 In terms of payer engagements, for 05, we have engaged in permitted payer discussions since April of last year. And the amount of payers that we've engaged with in a permitted fashion covers almost the majority of all commercial lives covered. 36:50 So, we've had great representation of introducing Axsome, as well as the clinical profile of 05 to all the payers, the potential payers in making decisions. 37:04 What I can tell you is that payers recognize that there's an unmet need in MDD, and they do recognize the novel mechanism of action associated with 05 and they're impressed by the clinical profile. Again, there are 20 MDD patients diagnosed right now. We see trends of that number continuing to increase. We know that two-thirds do not achieve remission and the clinical profile for AXS-05 is extremely compelling given the data package that we have with symptom reduction as early as one-week and achievement of remission in two weeks. 37:42 So, we're encouraged by the discussions that we've had with payers and look forward to tell anymore once we get approval.

37:51 Right. And then for AXS-07 just given the Phase 3 data, which showed superiority to triptan, how do you think this will be utilized and I guess and how are you positioning the marketplace?

38:09 Yeah. It's a great question. Thanks. So, I'll answer a question you didn't really ask, although you did ask in the last one and that's around how the discussions with payers are going? Those discussions have just recently commenced. And so, more to come on that. But what we do know is that payers recognize the dissatisfaction with current therapies, and the continuing cycling of patients. 38:36 To speak specifically to how we’re positioned within the [HCP market] [ph], it's a bit premature to speculate on that right now, but we’ll continue to hone in on the fact that the accelerator absorption and the speed of action for our product is, will be meaningful to both HCP’s patients and payers.

39:00 Alright. Thanks for taking the questions.

39:04 Thank you. Our next question comes from Jason [indiscernible] of Bank of America. Your line is now open. Please go ahead.

39:20 Hey, this is [Peri] [ph] on the line for Jason. Thanks for taking our question. Just quick question on ACCORD AXS-05 trial and the relapse rates, could you tell us how many patients this has been based on and I guess generally where the current enrollment is at, at this time? Just want to get a sense of how a change in trial design perhaps less patient seems to be enrolled or how that will impact the potential timeline of the trial? Thanks.

40:04 Hi. So, I'll start off before trying to get over to Amanda to answer the specific questions on a number of events and enrollment, but with regards to the timing of completion of the trial, we do not anticipate that that is going to change. Amanda?

40:28 Sure. So based on just enrollment alone, we on track for the planned readout of mid-next year. So, the key thing that we're looking at is obviously, you know we do have projections based on the number of relapses that we assume should be happening based on the study design. And so since we are below that number currently, what's kind of triggering our desire for consultation with the FDA.

41:01 Got it. Thank you.

41:07 Thank you.

41:08 Sorry, and just as a reminder, just to add to that, just remember that this is, we are referring to what's happening in the second part of the study, the randomized portion. All of these patients have previously received AXS-05 and have been stabilized on AXS-05 prior to randomization.

41:39 Our next question comes from Yatin Suneja of Guggenheim Securities. Your line is now open. Please go ahead.

41:49 Yeah, hi, this is Eddie on for Yatin. Thanks for taking my question. In terms of the label for 05, are their assumptions that you're looking under that may influence the launch preparations that you have ongoing? And would you disclose when and if the label discussions begin, given that those deficiencies that you respond to were precluding those discussions? And then assuming you can get an approval in the first half of the year, like, how should we think about 2022 revenues? How quickly can you penetrate this market and would you ever plan to provide revenue guidance in depression? Thanks.

42:23 So, a lot of questions there. So, before turning it to Lori to answer the question around assumption with regards to the label, in terms of disclosure of labeling discussions, we do think that that would be a definitive piece of information to be able to provide to the Street. So, that is our current thinking with regards to making you guys aware of that. 42:56 And then in terms of guidance for revenues for 2022, it's really premature for us to be providing revenue guidance on the product, the product is not yet approved. And also, we want to make sure that we understand what the label is, and which leads us into the question that you asked and with regards to labeling assumptions and I'll turn that over to Lori.

43:23 Yeah. Thanks for the question, Eddie. So, the best we could do in terms of commercial preparation is to prepare based off the label, the draft label that you submit to the FDA, which obviously is highly substantiated from the clinical trial results. 43:36 And so, we are preparing for that. I can imagine that major adjustments will be made to that label, but we are prepared to tweak, as fast as possible based on any labeling negotiations we get [there] [ph].

43:55 Can you just remind us what that proposed label language is?

44:02 So, what we’ve disclosed as you know is that the indication that we are going after is the treatment of MDD with regards to the specifics in the graphed label. Obviously, it would not be [proved first] [ph] to be disclosing that on the call.

44:24 Thank you.

44:28 Thank you. Our next question comes from Raghuram Selvaraju of H.C. Wainwright. Your line is now open. Please go ahead.

44:39 Thanks very much for taking my questions. Firstly, just quick clarification on the launch preparations timeline for both 05 and 07. Can you give us some additional clarity on assuming whenever you receive regulatory approval for those two drugs, what sort of lag would you expect to occur between the announcement of the approval and the actual commercial availability of product?

45:09 Thanks Ram for the question. So Lori, you want to take that?

45:12 Yes. So, hey, Ram. Thanks for the question. So, I think we’ve previously discussed and disclosed, you know it will likely be within one quarter after approval that we will launch.

45:26 In both cases, for both 05 and 07?

45:29 In both cases, yes.

45:31 Okay. Secondly, on the smoking cessation front, just two additional points of clarity there, that I was hoping you could provide. One is, in the discussion with the FDA, did they definitively indicate whether, top-line positive data from the clinical trial you are currently envisaging would be sufficient to support a supplemental NDA or if they indicated that even in the context of positive top-line data from this study, a second confirmatory study would be necessary in smoking cessation?

46:12 So, smoking cessation is a separate indication and two positive trials are required.

46:25 Got it. And did you get any color from the agency regarding their preferences with respect to what would constitute an appropriate control? And if this is an active control, what preferences they have if any?

46:48 So, given the product profile for AXS-05, as you know because it has two APIs in it, we do have to follow FDA's combination products rules. And so, we would have to demonstrate component contribution. So, one of the arms would likely have to be [indiscernible].

47:12 But no specific additional requirements or recommendations were provided by the agency beyond that. Is that correct?

47:24 Ram, I think as Amanda mentioned earlier, so we will provide the details of the design of the trial once we launched the study and that’s been our practice in the past and we're looking forward to finalizing the study design and then once we launch it, we'll be able to provide your details. We don't like to speculate prior to launching a study, because as you know, the design can change.

47:56 Understood. And then the last question is, with respect to the narcolepsy indication, if you have positive top-line data from the SYMPHONY trial, would that potentially constitute a circumstance under which you would be able to file the NDA right away?

48:15 So Ram, I'll turn that over to Amanda to comment on that.

48:19 Sure, thanks. Yes. If the SYMPHONY Study has positive results then that would be the basis of efficacy for our NDA. We do also have an ongoing [indiscernible] label study as well. So, that study is anticipated to complete approximately six months after conclusion of the SYMPHONY study.

48:47 Thank you.

48:52 Thank you. Our next question comes from Vikram Purohit of Morgan Stanley. Your line is open. Please go ahead.

49:03 Good morning, everyone. This is [indiscernible] on for Vikram. Thanks for taking our question. I was wondering if you could walk us to how the DCC platform works? What the metrics are that you have been testing I guess, on how you will monitor its utility in the real world setting?

49:25 Yes, please. I think that's a question for Lori.

49:28 If you like to answer, go ahead. We're very excited here, you can tell we’re arguing over who’s going to answer the question. Thanks for the question. So, first of all, let me just start out with why we we're excited about DCC. So, fundamentally, we believe that the goal of any engagement with ACP or patient is that it's meaningful and impactful. And in order to achieve that, what we did was design, a technology enabled platform that uses AI, machine learning, sophisticated data and analytics, really to synthesis data points that are collected and then deploy that to any Axsome touch point, whether that be with reps to ACP’s or for patients. 50:19 And the way that we came about developing this platform is that, we did fairly extensive research on understanding our audience and how they want to be engaged as well as research on the latest technology. And then that's why, and that's how we put the platform together. It is a highly integrated platform with several different systems to – but it is now seamlessly integrated. 50:48 In terms of KPIs and metrics and what we're planning for, because we believe that meaningful engagements that will have a higher impact with both physicians and patients, we do believe that the call points will be more. And given the digital nature of it, we do believe that it will be incredibly more efficient. 51:11 When we get close to approval or once we have approval and we start discussing salesforce size, I can give you more details around additional metrics that we'll be tracking.

51:32 Thank you. Our next question comes from the line of Myles Minter of William Blair. Your line is now open. Please go ahead.

51:45 Hey, thanks for taking the questions. Just on the call study for 05, have you disclosed what the definition of response to be randomized into the withdrawal portion is and also how you are classifying relapse? I know in ADVANCE, you used Cohen-Mansfield. I'm just wondering whether it's different here and whether or not a very stringent rate lapsed criteria on that scale is maybe what's driving the event right less than what you have predicted?

52:17 Sure. Amanda?

52:20 Sure. Thanks for the question. So, the response rate, we'll disclose that when we release the top-line results of the study. We do want to make note that, yeah, this study does include standard measures of Alzheimer's agitation. So, similar with some of the programs that are ongoing.

52:41 Okay. So, but the relapse measurement, is it safe to say that it is Cohen-Mansfield or is it just like a an event of agitation?

52:59 Yes, so there is formal definition which is driven by data driven definition. We're just – we'll be releasing the full formal definition at a later date.

53:13 Okay. Cool. And then I did not as obviously all on the review, and you've got to go talk to the FDA, but you are reiterating first half 2023 guidance in the press release, I was just wondering why that is? And I got your messaging that we expect that to change, but maybe just to the point of life, we don't know when that's changing too, so we just won't change it yet. I'm just curious as to why you restated that rather than withdrawing timing guidance here?

53:45 Yes. So, I think the reason for that is in giving our prior guidance. We did try to incorporate some buffer. And so currently, we don't see any reason to change that guidance, but we did want to alert folks to the fact that there may – it may change and that it is an active process and we do want to take advantage of the fact that we have this dialogue with the FDA. We want to make sure that the study design is appropriate, but for now, in terms of guidance, we don't see any reason yet to formally change it. 54:27 We will be coming back to you guys and providing an update as appropriate, but until then our guidance is our guidance.

54:39 Cool. Thanks for the questions.

54:44 Thank. Our final question comes from the line of David Hoang of SMBC. Your line is now open. Please go ahead.

54:55 Hey guys. Thanks for fitting me in here. I just had a question on the sales force for launching AXS-05 MDD, can you just remind us of the sales force numbers that you would expect are necessary to successfully support the launch in MDD? And then how are you, sort of managing expectations there with contingent offers given the unusual situation with the 05 review?

55:29 Yeah. Hi, David. Thanks for the question. So, we have not disclosed the number of sales reps that we're hiring just yet. But what I can tell you is that our personal promotion will cover 85% of the high prescribing physicians out there and that equates to roughly 23,000 HCP’s in the MDD space. Well, we will reveal salesforce size, the closer we get to improve our launch. 55:59 In terms of the contingent offers, I couldn't be more proud of the sale leadership that we have out in the field, we are – just to give you statistics that the field leadership that we hired in the field were operating on a less than 1% acceptance rate of applications to physicians. 56:22 So, we have the best of the best and what they've done over the past several months with the extended delay is really not only to build their team, but also to keep them highly engaged and excited about the opportunity.

56:40 Okay. Thanks so much for taking the question.

56:46 Thank you. That concludes today's question-and-answer session. I will now hand over to the management team for closing remarks.

56:56 Well, thank you all for joining us again on the call today. 2022 is a potentially pivotal year for Axsome with the potential for two new product approvals for depression and migraine, and also the distinct advancement of the rest of our industry leading CNS pipelines. So, all-in-all, we have four pipeline candidates being developing in six indications, which are either under FDA review or in late stage development. 57:23 We are committed to bringing these potential live changing medicines to people living with serious CNS conditions. We look forward to keeping you updated on our continued progress throughout the year. Have a great day.

57:43 This concludes today's conference call. You may now disconnect your line.