Axsome Therapeutics, Inc.

and welcome to today's AXA AXM fourth quarter and fall year 2021 financial results. My name is Candice and I will be your moderator for today's call. All lines will be muted during the presentation portion of the call with an opportunity for question and answer at the end. If you would like to ask a question, please press start followed by one on your telephone keypad. I would now like to pass the conference call over to our host, Mark Jacobson, Chief Operating Officer Mark, please.

Thank you, Operator. Good morning, and thank you all for joining us on today's conference call. Our earnings press release providing 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 axom.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 plans, commercial plans, 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 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. Ariel Tibuto, Chief Executive Officer, Nick Pizzi, Chief Financial Officer, Lori Engelbert, Senior Vice President of Commercial and Business Development, and Dr. Amanda Jones, Senior Vice President of Clinical Development. Ariel will first provide an overview of the company and then review recent developments and upcoming milestones. Following Ariel, 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. And with that, I will turn the call over to Ariel.

Thank you, Mark. Good morning, everyone, and thank you all for joining Axiom Therapeutics' fourth quarter and year-end 2021 financial results and business update conference call. 2021 was a 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. 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, AXS05, 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. 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. AXS05 is also being developed for the treatment of Alzheimer's disease agitation. Enrollment in the Phase III ACCORD trial for this indication is progressing. 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 this study and will provide an update following consultation with the FDA. With regards to the development of AXS05 in smoking cessation, we intend to provide timing on initiation of that trial in the coming months. Moving on to our second lead product candidate, AXS07, a multi-mechanistic acute treatment for migraine. The NDA for AXS07 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. We have since been informed by the FDA that it does not anticipate any issues with completing this facility inspection prior to PDUFA. With the NDAs for AXS05 and AXS07 under active review, Axome launch preparations are underway, and Laurie will provide details on our commercial launch readiness. The rest of our rich pipeline continues to advance. For AXS12, 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. 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. I will now turn the call over to Lori, who will provide a commercial update.

Thank you, Ariel, 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. 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. 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 undeniably urgent need to help address this burden and bring support to those affected by the disease. Our approach to commercialization for AXS05 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 AXM immediately upon approval. The market access team continues to engage in permitted payer discussions, ensuring awareness of Axiom 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. If approved, AXS05 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. I will now shift gears to address launch preparations for AXS07 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. 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. Permitted payer discussions have commenced and Salesforce recruiting is underway. Consistent with the AXS05 sales rep offers, all offers for the AXS07 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 migraines. 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. 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. The differentiated clinical profiles for both AXS05 and AXS07 have the potential to bring significant benefit to patients and physicians who treat them. We remain excited about the opportunity to potentially bring these important new products to market. I will now turn it over to Nick, who will review our financials.

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. Inclusive of utilization of our ATM facility in Q1 2022, our pro forma 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. 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. 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 and personnel expense, along with an increase in non-cash stock compensation expense. 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. 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. 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 AXS05 in MDD and AXS07 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 AXS05 and AXS07. We believe our year-end pro forma 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. 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.

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

Thank you. If you would like to ask a question, please press one star followed by one on your telephone keypad. If for any reason you'd like to remove your question, please press star followed by two. Again, to ask a question, it is star followed by one. As a reminder, if you are using a speakerphone, please remember to pick up your handset before asking your question. Our first question. comes from the line of Charles Duncan of Cantor Fitzgerald. Your line is now open. Please go ahead.

Hi, this is 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?

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

Good morning. So the current snapshot is, as you're aware, we were made of two deficiencies pertaining to CMC and, in particular, analytical methods a number of months ago. We subsequently responded to those deficiencies, addressing them. And FDA has confirmed receipt of those, acknowledged receipt, and has told us they are reviewing our responses. 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. And so, again, that's not guidance. We haven't been told by FDA that that's the process or procedure they're using, but that's what we're using just for planning purposes. So hopefully that's helpful.

Yep. 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?

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 and 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, you know, 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. 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 XSO5, and so we want to make sure that we're looking at the study very carefully.

Okay. And switching gears, and last question for 07. Given the treatment landscape for migraine with oral CGRP drugs and taking share from the tryptans as well as the CGRP monoclonals, can you help us understand the residual unmet need and product positioning?

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 showed that 70% of patients are still dissatisfied with the current therapies available. And to give you a further data point that I think was fairly poignant in 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 isn't lost on me, that cycling through that many therapies means that there's for sure a continued high-level dissatisfaction. And again, that was done as recently as a year ago. And I also just want to make mention that Triptans 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.

Thank you for taking our questions.

Thank you. Our next question comes from June Lee of Trusted Securities.

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

Hey, Jonas, it's Mark. So, you know, 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, you know, why do we think about it like that? Because, you know, again, during the course of a normal review, if you have a substantive addition, amendment, or additional data, analyses, etc., that FDA accepts to review. 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, two to three months, depending on the nature of the content. So if you go on to the FDA's website and check out their guidance, the death reference manual and things like that, it gives you categories of what triggers, say, a two-month or a three-month. We're just assuming, for planning purposes, given the timeline extension at play, given that there's no PDUFA clock, we're assuming that three months is, you know, why is it three months? Because that's typically the time that FDA has determined they need in order to review additional data. 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 three months? We don't know. We haven't, again, we haven't received that information. specific feedback that they're going to take action in three months from our submission. That's not what it is. But we think it's, you know, 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. So no other references for you besides, you know, standard FDA processes and procedures.

Understood. That's fair. And thank you so much. That's helpful. And then one more question. With 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 drug having a greater than anticipated effect. And then you're looking to have a dialogue with the FDA for potential trial amendment. What kind of amendment did you have in mind? Is this an interim look? and an interim analysis so that for possibility of a security at interim. We'd love to hear your elaboration on what you hope to accomplish with the meeting with the FDA on the court. Thank you.

Yeah, so June, thanks for the question. So the reason why we mentioned that is when you conduct and design a randomized withdrawal study, the timing of when you stop that study is kind of up in the air. It depends on the number of events, as opposed to a standard parallel group design where the study might be, let's say, five weeks or six weeks in duration. And so we do watch the event rate carefully. And also, typically, the way that those parameters are set out 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. 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, We 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.

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

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

Great. Thank you.

Thank you.

Thank you. Our next question comes from Vimal Devan of Monzo Securities. Your line is now open. Please go ahead.

Okay, yeah, thanks for taking the question then and for the update. So one thing just to clarify, because we get this question a lot when trial is ongoing and the events are not accruing the way initially expected. So just to be clear, so you don't know, you have no sense of whether it's fewer events in the treatment arm or potentially fewer events in the placebo arm or both, just to be clear, right? So obviously if it's fewer events in the treatment arm, that's good, but at this point you just don't know. So if you could just clarify that, because we're getting a couple questions I want to make sure. That's clear. 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, Pat, sort of the stake with the FDA, where you did not receive sort of an official CRL, but there's been sort of the back and forth dialogue. So I'm just wondering if you've received any other further insights from the FDA, sort of why this unusual path is taking place. Is there, you know, why wasn't there sort of more formal discussions you know, communication and actual announcement, and then maybe an official push out of the action, which would probably be helpful for your planning purposes as well. So 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. Sure. Sure. I'll let Amanda answer the first question, and then we'll address the second question.

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

So, that's... And then with regards to the further insights into why the FDA delayed We don't really know. What we do know that has been publicly discussed is and which also is reflective of what's been happening with other Purdue for Gold in general in the industry is there is a capacity, a resource constraint at the FDA. Could that be contributing to this particular situation? 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. So we're happy that they have continued to review the NDA. And with regards to the CMC deficiencies, 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.

Okay, thank you.

Thank you. Our next question comes from Mark Goodman of SBD LearLink. Your line is now open. Please go ahead.

Yes, good morning, Ariel. Can you talk about just on those, I got a couple of questions. On 07, first of all, has the FDA done the manufacturing inspection yet? Have they told you that there's a date if they haven't done it yet?

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

Right. but have they done it yet?

Yeah, so in the typical course of an NDA review, we made an exception with XSO5 in the unusual situation. We refrain from providing the back and forths, but what we have disclosed is 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, that that is no longer an issue.

Have you started labeling discussions on that product yet?

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

Well, then maybe we can just flip to 05. And when did you file your response exactly to FDA so we can know when that three months in your head, you know, the clock started in your head?

Hey, Mark, 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 acknowledgement of receipt and confirmation of review. And that's around the time we 8K'd that, which I think was like mid-January. And that is, you know, that's how we're thinking about I guess you could say like potential... Well, for planning purposes. For a 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.

Right. So has there been any type of labeling negotiations on this product? Or were you not comment on that either?

So Mark, for AXS05, 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.

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 questions related to the hunger issue?

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

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?

Yeah, so I'll turn that over to Amanda.

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, you know, 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 periods.

And this is going to start when?

We intend to provide further guidance on initiation of a study within the year. Okay, thanks.

Thank you. Our next question comes from Joseph from Cohen and Company. Your line is now open. Please go ahead.

Hi there. Good morning, and thank you for taking my questions. Maybe for the AXS05 review, I know you highlighted 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 that I would follow.

So we did make the FDA aware of 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.

Okay. And then on the AXS07 review, are the analytical concerns that popped up with AXS05 applicable to AXS07? Did you have to make any changes there or is that specific to AXS05?

That was specific to AXS05, so we don't see any direct connection between the two.

Okay, perfect. And then maybe just last one on the Alzheimer's agitation update. I guess, how consistent are agitation symptoms between patients? Are we now hitting a point where it's just been too long for too many patients? Or is it common that you're going to have patients that have less severe disease and maybe just wouldn't have had an agitation relapse without treatment? How consistent is disease here?

There definitely is variability in the symptoms of the disease. So patients who have Alzheimer's disease who are agitated, they may have a range of symptoms. So, for example, one of the common symptom scales, the Kwan-Manfield Agitation Inventory has 29 items. So, in each of those items corresponds to a separate behavior. And so, and those behaviors are clustered into different groups. And, you know, so that reflects the variability in the presentation. So agitation can be manifested in different ways depending on the patient. Okay, thank you.

Thank you. Our next question comes from the line of Matt Kaplan of Ladenburg and Fellman. Your line is now open. Please go ahead.

Hi, good morning. I just wanted to shift topics a little bit. It's maybe for Lori. Can you talk a little bit about your commercial prep and specifically how your interactions have been going with payers and discussions for 05 and 07 on the payer front?

Yeah. Hi, Matt. Thanks for the question. So as I stated in the prepared remarks, commercial prep for 05 is we are we are ready to go. And 07 is well on its way, tracking accordingly to potential launch plans. 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 life's covered. So we've had great representation of introducing Axiom as well as the clinical profile of O5 to all the potential payers in making decisions. What I can tell you is that payers recognize that there is an unmet need in NDD, and they do recognize the novel mechanism of action associated with O5, and they're impressed by the clinical profile. Again, you know, There are 20 million MBD 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 AXS05 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. So we're encouraged by the discussions that we've had with payers and look forward to telling you more once we get approval.

And then for XS07, just given the Phase 3 data, which showed superiority to Triptan, how do you think this will be utilized, I guess, and how will you position in the marketplace?

Yeah, it's a great question. Thanks. So I'll answer a question you didn't really ask, although you did ask it in the last one, and that's around how the discussions with payers are going. Those discussions have, you know, just recently commenced. And so, you know, 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. To speak specifically to how a position within the HCP market, it's a bit premature to speculate on that right now. But, you know, we continue to hone in on the fact that, you know, the accelerated absorption and the speed of action for our product will be meaningful to both HCPs, patients, and to payers. All right.

Thanks for taking questions.

Thank you. Our next question comes from Jason Gerberoy of Bank of America. Your line is now open. Please go ahead.

Hey, this is Perry on a line for Jason. Uh, thanks for taking our question. Uh, just quick question on, uh, accord, um, accessible five, uh, uh, trial and the relapse rates. Could you, um, could you tell us how many patients, um, this was, this has been based on, and I guess generally what the, um, where the current enrollment is at at this time. Um, just want to get a sense of, uh, you know, how. a change in trial design, perhaps less patients needed to be enrolled, how that'll impact the potential timeline of the trial. Thanks.

Hi, yeah, so I'll start off before turning it over to Amanda to answer the specific questions on number of events and enrollment. But with regards to the timing of of completion of the trial, we do not anticipate that that is going to change. So, Matt.

Sure. So, you know, based on just enrollment alone, we are, you know, on track for, you know, the plan readout of, you know, 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 since we are below that number currently, what's kind of triggering our desire for consultation with the FDA?

Got it. Thank you.

Thank you. 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 XSO5 and have been stabilized on XSO5 prior to randomization.

Our next question comes from Yatin Sunja of Guggenheim Securities. Your line is now open. Please go ahead.

Yeah, hi. This is Eddie on for Yatin. Thanks for taking my question. In terms of the label for O5, are there assumptions that you're working 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, 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.

So a lot of questions there. So before turning it to Laurie to answer the question around assumptions 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. 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, you know, we want to make sure that we understand what the label is, which leads us into the question that you asked with regards to labeling assumptions, and I'll turn that over to Lori.

Yeah, thanks for the question, Eddie. So, you know, the best we can do in terms of commercial preparation is to prepare based off the label, the draft label that you submit. to the FDA, which, you know, obviously is highly substantiated from the clinical trial results. And so we are preparing for that. I can't imagine that, you know, major adjustments will be made to that label, but we are prepared to, you know, tweak as fast as possible based on any labeling negotiations we get back.

Please remind us what that proposed label language is.

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 draft label, obviously it would not be prudent for us to be disclosing that on a call.

Thank you.

Thank you. Our next question comes from Ram Selvaju of HD Wainwright. Your line is now open. Please go ahead.

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.

Oh, thanks, Ron, for the question. So, Laura, you want to take that?

Yeah, so, hey, Ron. Thanks for the question. So, you know, I think we've previously discussed and disclosed, you know, it will likely be within one quarter after approval that we will launch.

In both cases, for both 05 and 07?

In both cases, yes.

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.

So smoking cessation is a separate indication and two positive trials are required.

Got it. 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?

So given the product profile for XSO5, 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 foreground.

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

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

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?

So, Ron, I'll turn that over to Amanda to comment on that.

Sure, thanks. So, yes, you know, if the symphony study has positive results, then that would, you know, be, you know, the basis of efficacy for our NDA. We do also have an ongoing open label study as well, and so that study is anticipated to complete approximately six months after conclusion of the symphony study.

Thank you.

Thank you. Our next question comes from Vikram Porohit of Morgan Stanley. Your line is now open. Please go ahead.

Good morning, everyone. This is Gospel on for Vikram. Thanks for taking our question. I was wondering if you could walk us through how the DCC platform works, what the metrics are that you have been testing against, and how you will monitor its utility in the real world setting.

Yeah, please. I think that's a question for Laurie.

If you'd like to answer this, 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. First of all, let me just start out with why we're excited about DCC. Fundamentally, we believe that the goal of any engagement with an HCP 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 analytics, really to synthesize data points that are collected and then deploy that to any axiom touchpoint, whether that be with reps to HCPs or for patients. 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 that's how we put the platform together. It is a highly integrated platform with several different systems, but it is now seamlessly integrated. 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 effective. And given the digital nature of it, we do believe that it will be incredibly more efficient. 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.

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

Hey, thanks for taking the questions. Just on the Accord study for 05, have you disclosed what the definition of response to be randomised into the withdrawal portion is and also how you're 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 relapse criteria on that scale is maybe what's driving the event rate less than what you had predicted before.

Sure. Amanda?

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

Okay. So, the relapse measurement Is it safe to say that it is Colin Mansfield or is it just like an event of agitation?

Yeah, so there is a formal definition which is driven by data-driven definition. We'll be releasing the full formal definition at a later date.

Okay, cool. And then I did notice, obviously, it's all under review and you've got to go talk to the FDA, but you are reiterating first half 23 guidance in the press release. I'm just wondering why that is. And I gather your messaging that we expect that to change, but maybe just for the point of like, we don't know when that's changing to, so we just won't change it yet. I'm just curious as to why you restated that rather than withdrawing timing guidance here.

Yeah, 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 It may change in 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. We will be coming back to you guys and providing an update as appropriate. But until then, our guidance is our guidance. Cool.

Thanks for the questions.

Thank you. Our final question comes from the line of David Hogg of SMBC. Your line is now open. Please go ahead.

Hey, guys. Thanks for fitting me in here. I just had a question on the sales force for SMBC. launching AX05 and MVD. Can you just remind us of the Salesforce numbers that you would expect are necessary to successfully support the launch in MVD? And then how are you managing expectations there with contingent offers given the unusual situation with the 05 review?

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 positions out there. And that equates to roughly 23,000 HCPs in the NDD space. We will reveal Salesforce size the closer we get to approval and launch. In terms of the contingent offers, I couldn't be more proud of the field leadership that we have out in the field. You know, we are, you know, just to give you a statistics that the field leadership that we hired in the field were operating on a less than 1% acceptance rate of applications to positions. 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.

Okay. Thanks so much for taking the question.

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

Well, thank you all for joining us again on the call today. 2022 is a potentially pivotal year for Axome, with the potential for two new product approvals for depression and migraine, and also the continued advancement of the rest of our industry-leading CNS pipelines. So all in all, we have four pipeline candidates being developed in six indications, which are either under FDA review or in late-stage development. We are committed to bring these potentially life-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.

This concludes today's conference call. You may now disconnect your lines.