Q4 2021 Axsome Therapeutics Inc Earnings Call

Candice: Good morning, and welcome to today's AXA, and AXAM 4th quarter and 4 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 questions and answer at the end.

Good morning.

And welcome to today's Axa, some fourth quarter and full 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.

Candice: 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, his operating officer. Mark, please...

If you would like to ask a question. Please press star followed by one on your telephone keypad.

I'd now like to pass the conference call labor to our highest.

Marc Jacobs sudden cheap.

Operating officer Mark <unk>.

Thank you operator, good morning, and thank you all for joining us on today's conference call.

Mark Jacobson: 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. 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 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 statement.

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 <unk> Dot 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.

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.

<unk> plans and possible intended use of cash and investments.

These forward looking statements are based on current information.

Functions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward looking statements.

These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports.

You are cautioned not to place undue reliance on these forward looking statements, which are only made as of today's date and the company disclaims any obligation to update such statements.

Joining me on the call today are Dr. Ariel Buteau, Chief Executive Officer.

Nick Peasy, Chief Financial Officer, Lori Inglebert, Senior Vice President of commercial and business development and Dr. Miller Jones Senior Vice President of critical development.

Area will first provide an overview of the company and then review recent developments and upcoming milestones following area 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.

So I will turn the call over to Ariel.

Herriot Tabuteau: These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Lori Englebert, Senior Vice President of Commercial and Business Development; and Dr. Amanda Jones, Senior Vice President of Clinical Development.

Thank you Mark good morning, everyone and thank you all for joining axon 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.

Herriot Tabuteau: Ari 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 Ari. Thank you, Mark. Good morning, everyone.

I will provide an update on our development pipeline before turning it to Laurie who will provide a commercial update.

Herriot Tabuteau: And thank you all for joining Axsome 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, AXS 05, which is undergoing an NDA review for the treatment of major depressive disorders. The FDA previously informed us of two deficiencies related to analytical methods in the chemistry, manufacturing, and controls section of the NDA.

Starting with our first lead product candidate, except so five which is undergoing an NDA review for the treatment of major depressive disorder.

The F D. A previously informed us of two deficiencies related to analytical methods and the chemistry manufacturing and controls section of the NDA.

Herriot Tabuteau: We submitted a response addressing these decisions. 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 3 Accord Trial for the syndication is progressing, and currently, blinded relapse events are below projection.

We submitted our 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.

Okay. So five is also being developed for the treatment of old timers disease agitation.

Enrollment in the phase III core trial for this indication is progressing.

Currently blinded relapsed events are below projections.

Herriot Tabuteau: 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 regard to the development of AXS05 in smoking cessation, we intend to provide timing for the initiation of that trial in the coming months. Moving on to our second lead product candidate, AX07, a multi-mechanistic acute treatment for migraines.

This may imply 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 in excess of five and smoking cessation, we intend to provide timing on initiation of that trial in the coming months.

Moving on to our second lead product candidate <unk>.

So seven multi mechanistic acute treatment for migraine.

Herriot Tabuteau: The NDA for XSO7 was accepted for review by the FDA with a PDUFA target action date of April 30, 2022. However, 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 that date. We have since been informed by the FDA that it does not anticipate any issues with completing this facility inspection prior to production, with the MBAs for AXS05 and AXS07 under active review. Thank you. Axsome launch preparations are underway, and Lori will provide details on our commercial launch radio. Meanwhile, the rest of our rich pipeline continues to advance.

The NDA for excess of seven was accepted for review by the FDA with a <unk> target action date of April 32022.

He previously notified us that due to COVID-19 related travel restrictions.

Might be unable to complete the required inspection of the contract manufacturing facility prior to the Paducah date.

We have since been informed by the FDA that it does not anticipate any issues with completing this facility inspection prior to Purdue pharma.

With the N D AIDS for excess so five any excess or seven under active review.

Axon launch preparations are underway.

And Lori will provide details on our commercial launch readiness.

First of all rich pipeline continues to advance for excess 12 hour product candidate being developed for the treatment of narcolepsy.

Herriot Tabuteau: For AXS 12, our product candidate being developed for the treatment of narcolepsy, enrollment in the Symphony Phase 3 trial is progressing, and top-line results are anticipated in the first half of 2023. For AXS14, 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, Herriot, and good morning, everyone.

Enrollment in our Symphony Phase III trial is progressing and top line results are anticipated in the first half of 2023.

For excess 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 Laurie who will provide a commercial update.

Thank you area and good morning, everyone.

Lori Englebert: 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 persistent and increasingly serious global crisis of depression.

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.

<unk> 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, he global health crisis.

The appointment 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.

Lori Englebert: 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 AXS-05 is innovative and purposeful, and we are prepared to execute AVA proof. Field leadership remains excited and has fully recruited the field force, all of whom are ready to join Axsome immediately upon approval.

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 excess that's five it's innovative and purposeful and we are prepared to execute if approved.

Failed leadership remains excited and have fully recruited the field force all of whom are ready to join axon immediately upon approval.

Lori Englebert: The market access team continues to engage in permitted payer discussions and Share 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. If approved, AXSO5 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.

The market access team continues to engage and permitted payer discussions and sharing 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 it.

The five 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.

Lori Englebert: I will now shift gears to address March preparations for AXSO7 for the acute treatment of migraine. Despite recent innovation, there continues to be a close to 70% dissatisfaction rate with currently available therapies, demonstrating high unmet need for the 37 million Americans who experience migraine.

I will now shift gears to address notch preparations for excess of seven 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 with a 37 million Americans who experience migraine.

Lori Englebert: 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 field force recruiting is underway. All offers for the AXSO7 self-source will be made contingent upon approval. We are excited about the opportunity to potentially bring another option to market another option for the many Americans suffering from migraines.

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 field force recruiting is underway.

Consistent with the access of five sales Rep offers all offers for the excess of seven sales force 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.

Lastly.

Lori Englebert: 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.

Our digital centric commercialization or D. C. C platform remains fundamental to the commercialization strategy the.

The D C C platform as a technology enabled platform designed to use streamline 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 of innovative and purposeful with the intent to bring important new products to market in a meaningful way.

Nick Pizzie: The differentiated clinical profiles for both AXS05 and AXS07 have the potential to bring significant benefits 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 finances. 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.

The differentiated clinical profiles for both excess of five and access of seven has 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.

Nick Pizzie: 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.

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 are 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 onetime charge of $10 $2 million related to the Pfizer license agreement.

Nick Pizzie: 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 expenses, along with an increase in non-cash stock compensation expenses.

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 noncash stock compensation expense.

Nick Pizzie: 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. The 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. The 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.

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 <unk> 90 per share for the three months ended December 31, 2021, compared to a net loss of $29 2 million or <unk> 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.

Nick Pizzie: 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.

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 the excess of five and M. D. D N a excess of seven in migraine and access to an additional 130.

Million dollars thereafter.

This committed non dilutive capital that gives us additional financial flexibility through both anticipated potential commercial launches for access so five in excess of seven.

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 'twenty 'twenty four.

Mark Jacobson: 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. Thank you, Nick.

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.

Operator: Operator, may we please have our first question? Thank you. If you would like to ask a question, please press 1. 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 Canter Fitzgerald. Your line is now open. Hi, this is Pete Stavropoulos on behalf of Charles.

Thank you Nick operator May we please have our first question.

Thank Kim 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's a star followed by one as a reminder, if you like using a speakerphone. Please remember to pick up your handset before asking your question.

Yeah.

Our first question comes from the line of Chiles Duncan of Cantor Fitzgerald. Your line is now open. Please go ahead.

Hi, This is a piece of the rock Lasantha draws on good morning, and congratulations on all the progress.

Yeah.

Pete Stavropoulos: Good morning, and congratulations on all the progress. My 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? Great, thank you for the question. Now I'll turn it to Mark to talk about regulatory communications and interactions with the FDA.

First question is 400.

Can you provide any color on the next steps with the SBA and anticipated.

Has there been any other dialogue with the FDA related to anything about efficacy or safety or anything else.

Alright. Thank you for the question so I'll turn it to Mark to talk about your regulatory.

Communications and interactions with the FDA it.

Mark Jacobson: So, you know, the current Snapshot is, as you're aware, we were made aware 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 documents, acknowledged receipt of them, 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.

It would be good morning so.

The the current.

The upshot is as you're aware we are made of two deficiencies pertaining to CMC and in particular analytical methods and number of months ago. We subsequently responded to those efficiencies addressing them.

And FDA has confirmed receipt of those acknowledged receipt and has told US. They are reviewing our responses. So that 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.

Mark Jacobson: And as that progresses, 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 you know as that proceeds will continue to keep you updated in terms of how we're thinking about timing. We we don't have any guidance for you or for specific feedback that we've received.

So what we're doing for planning purposes.

As we're using kind of a major amendment framework to inform our planning processes and.

Mark Jacobson: And just as a reminder 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 our 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, yeah.

Just as a as a reminder to that during the course of a normal review. If there is a major amendment submitted that F. D. A except to review that typically extends the paducah clock by three months.

In total and so again that that's our 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 just for planning purposes. So hopefully that's helpful.

Thank you and.

Herriot Tabuteau: Thank you. For 05 in Alzheimer's education, can you give us a sense of how enrollment is going, and has there been any impact from COVID? Thanks for the question. Enrollment is proceeding well, and it puts us on track to meet our guidance for the first half of 2023 in terms of reporting results.

0005 in Alzheimer's agitation can you give us a sense of how enrollment is going and has there been any impact by COVID-19 .

Joe Thanks for the question enrollment is proceeding well and it puts us on track to.

To meet our guidance of the first half of 2023 in terms of reporting results. We did discuss in the release this morning that.

Herriot Tabuteau: We did discuss in the release this morning that, The target number of events is lower than our projections because it implies potentially greater than expected durability of effect. But it does, makers 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. We're very excited that this is pioneering work that we are conducting, and this is the first time that this study design has been used in the syndication for Alzheimer's disease agitation with AXS05.

The the target number of.

Of events, which are which determines actually when we'd be able to stop the study, but that is a it's a good thing that that that those events are lower than our projections because it implies potentially a.

Greater than expected durability of effect, but it does makers 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 this indication and consult with them.

We're very excited that this is a pioneering work, which we are we are.

Conducting and this is the first time that this study design has been used in the syndication with in Alzheimers disease agitation with the excess so five and so while we want to make sure that we're looking at the study very carefully.

Lori Englebert: And so we want to make sure that we're looking at this study very carefully. And switching gears and last question for 07, given the treatment landscape for migraine with oral CGRP drugs and taking share from the Triptans 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.

Okay.

And switching gears last question 0407, given the the treatment landscape for migraine with oral <unk> drugs and are taking share from other defense.

Well as the seed European monoclonal or can you help us understand the residual unmet need and our product positioning.

Lori Englebert: Thanks for the question. The migraine landscape continues to have a high unmet need. Recently, as recently as a year ago, CHAMP, a well-known patient advocacy organization, conducted a very extensive survey that 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, that survey revealed that 55% of migraine patients have cycled through at least 10 different therapies.

Yeah, Hi, I'm 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, Oh, well known patient advocacy organization performed a very extensive survey which showed that 70%.

Some patients are still dissatisfied with the current therapies available and to give you. A further data point that I think was fairly a poignant and driving that point home is that that survey revealed that 55% of migraine patients have cycled through at least 10 different therapies are it's a it's a it's a point that.

Lori Englebert: 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 of dissessive status. And again, that was done as recently as a year ago.

That isn't lost on me that that cycling through that many therapies means that there is for sure a continued high level just acid satisfaction and again that was that was done as recently as a year ago and I also just wanted to make mention that triptans are still 85% of the market share them out at and in the current treatment landscape.

Lori Englebert: And I also, you know, just want to make mention that trip hands are still 85 percent of the market share out in the current treatment landscape. We do think that given our clinical profile, there's great potential for the product. Thank you for taking our questions. Thank you.

We do think that given our clinical profile there, there's a a great potential for the product.

Thank you for taking our questions.

Yeah.

Thank you.

Dune Lee: Our next question comes from Dune Lee of Trust This 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? And can you share any references supporting that assumption?

Our next question comes from Joon Lee of Trust the Securities.

Hey, guys. Thanks for taking my questions and thanks for the updates.

So just to summarize our response to the prior question your working assumption based on what you call them Major Amendment framework is a three month extension on the produce side is that correct and can you share any references supporting that assumption.

Mark Jacobson: Hey June, it's Mark. So, don't take this as written in stone. We're just using this for something to allow us to run the business and for planning purposes. Why do we think about it like that?

Hey, Jonas it's Marc so so.

Don't take that as a written in stone, where we're just using that for something to allow us to run the business and for planning purposes.

Why do we why do we think about it like that because you know again during the course of a normal review. If you are a substantive addition amendment or additional data analyses et cetera that FDA accepts to review right. They can if they accept to review it as a major amendment and then depending on what you submit the clock can be extended by.

Mark Jacobson: Because again, during the course of a normal review, if you have a substantive addition, amendment, or additional data, analyses, et cetera, that FDA accepts to review, 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 delay. 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 three months is... Why is it three months?

But it's a two to three months depending on on on the nature of the content. So.

If you go onto to the Fda's website and check out their guidance you know that the death reference manual things like that it gives you categories of what trigger let's say a two month or three month in and we're just assuming for planning purposes, given the timeline extension that play given that Theres no Purdue four o'clock, we're assuming that that.

Three months is is why is it three months because that typically the time that FDA has determined they need in order to review additional data. So it's similar here, but were just off the clock and so that 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 that specific feedback that.

Mark Jacobson: 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 behind it, and is it going to be three months? We don't know. Again, we haven't received that 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'

That theyre going to take action in three months from our submission that's not what it is but we think it is.

Mark Jacobson: In the 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, no other references for you. Besides, you know, standard FDA processes. Understood. That's fair.

In absence of any direct commentary like that that that's what we're using because that that's information that FDA has provided publicly in terms of the normal course of review.

So no no other rebate that's for you but.

Besides the standard FDA processes and procedures.

Joon Lee: And thank you so much. That's helpful. And then one more question. With regard to your accord study in Alzheimer's agitation, you're seeing a lower event in Rob Relapse, then you project it, and then you're implying that that could be due to the 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

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 Youre seeing.

Lower events.

Relapsed than you projected and then you're implying that that could be due to drug having a greater than anticipated effect and then you are 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 or possibility of a security at NRT.

We'd love to hear your elaboration on what you hope to accomplish with that.

Meeting with the FDA on thank you.

Herriot Tabuteau: Is this an interim look and an interim analysis so that there is the possibility of a superiority at interim? We would love to hear your elaboration on what you hope to accomplish, meeting with the FDA on the court. Thank you. Yeah, so, Joon, thanks, thanks for the question. So, the reason why we, what we mentioned is that when you conduct and design a randomized withdrawal study, the timing of when you stop that study is kind of up in the air.

Yeah. So so joon. Thanks. Thanks, Thanks for the question so.

The reason why we are why we mentioned that is when when you.

Conduct and design of rent randomized withdrawal study eat the 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 lets say five weeks or six weeks in duration.

And so we do watch.

The event rate are carefully and and also Tim.

Herriot Tabuteau: And so there's very little in terms of precedent. So, you know, 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 inappropriate study design. When can we expect an update on that? This is something that we would expect to provide to the street fairly quickly, so this is an active As you know, the study is ongoing, and we do have an open dialogue with the FDA on the indication.

Typically the way that that those parameters are set out.

Prospectively is is that it's based on prior.

Prior information you know with a particular indication in the case of old timers disease agitation. There currently is no product that is approved.

And and so so theres very little in terms of in terms of precedent. So what 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 we look at the design very carefully and that are we.

We we dialogue with the FDA to make sure that this is a N.

Appropriate study design.

But when can we expect an update on that thank you.

Right.

Okay.

This is something that that we would expect to provide to the street are fairly quickly. So is this 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.

Yeah.

Great. Thank you.

Thank you.

Yeah.

Thank you.

Vimal Diwan: Thank you. Thank you. Thank you. Our next question comes from Vimal Diwan of Munso Securities. Your line is now open, please go ahead.

Our next question comes from the multi ban of months Securities.

Your line is now open. Please go ahead.

Vimal Diwan: Okay, yeah, thanks for taking the questions and for the update. So one thing just to clarify, because we get this question a lot. 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, the stake with the FDA, where you do not receive sort of an official CRL, but there's been sort of this back and forth dialogue.

Okay, Yeah, thanks for taking the questions and for the update so one thing just to clarify because we get this question a lot.

Ongoing and events are not accruing the way.

Do you expect it to so just to be clear. So you don't know.

No sense of whether it's fewer events in the treatment arm or potentially fewer events in the placebo arm or boat well just to be clear. It's obviously, if it's fewer events in the treatment arm is good but at this point you just don't know so if you could just clarify that because we're getting a couple of questions I want to make sure that.

That's clear and then my second question going back to the old five discussion on M. D D.

Being confusing.

I think for you and for all of Us.

Sticking with the FDA, where you did not receive certain official.

But there's been some back and forth dialogues and I'm just wondering if you've received any other further input from the FDA. So why does the unusual part taking.

Vimal Diwan: So I'm just wondering if you've received any other further insights from the FDA, so why this unusual path? 8- Handicap, 7-Fifth August, Corinne DeWayne- tells göstowao as bardzo komunikacje polskiej. Syszaem dzisiaj mona byo zauway t krcack apk started.

Taking place there.

It wasn't there something more formal.

Communication.

Actual announcement and then maybe a official pushed out of the action.

Amanda Jones: a Rahul mona byo si domyci, bo w bardzo krótkich, sufferuli rówach, ouch. Sure, I'll let Amanda answer the first question and then we'll address the second question. So, the relapse rate that we're looking at is blinded. We don't know which treatment arm that relapses are occurring in, and then with regard to further insights into why the FDA delayed. We don't really know.

That would be helpful for your planning purposes as well. So I'm just curious if you have any other thoughts on why it's gone. This route as opposed to what we've seen previously.

Yeah.

Sure sure I'll, let I'll, let Amanda and so the first question and then we'll address the second the second question sure. So thanks for the question. So the relapse rate that we're looking at it its blinded. So this study and that study period is fully behind it. So we don't know which treatment arm that relapses are occurring.

So.

Yes.

Yeah.

And then with regards to the.

Amanda Jones: What we do know that has been publicly discussed and which also is reflective of what's been happening with other PDUFA goals in general in the industry is that there is a capacity and a resource constraint at the FDA. Could that be contributing to this particular situation?

Further insights into.

Why do you have to you to like we don't really know what we do know that 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. As you know there was a capacity resource constrained at the FDA could that be contributing to this particular situation.

Amanda Jones: You know, 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. So we're happy that they have continued to review the NDA. And, with regard 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.

You know, perhaps what we are focused on is making sure that we respond to the FDA as quickly as possible.

The best possible fashion to allow them to continue the review of the NDA. So we're happy that our but they have continued to Richard 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 and you know our team was able to respond to that.

So we will continue to do that currently there are no open items is as Mark mentioned.

Okay.

Okay. Thank you.

Thank you.

Mark Goodman: 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.

Our next question comes from Marc Goodman of S. P. D Link your line is now open. Please go ahead.

Ari Maizel: Can you talk about just 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 regard to O7, what they have told us is that completing the inspection by the PDUFA date will not be an issue. But have they done it yet?

Yes. Good morning area can you talk about just on those I got a couple of questions. I know seven first of all have as the SBA done the manufacturing inspection yet have they told you.

That there's a day if they haven't done it yet.

Hmm.

So with regards to show seven what they have told US is that completing the inspection by the <unk> date will not be an issue.

Right.

But have they done it yet.

Ari Maizel: Yeah, so in the typical course of an NDA review, you know, we made an exception with XS05 in the unusual situation; we refrain from providing the back and forth. But, you know, what we have disclosed is that 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 is no longer an issue.

Yes, so in the typical course of a of an NDA review.

We made an exception with access to a five year in the unusual situation we.

We refrain from providing the back and forth but.

We have disclosed is that the FDA has told us directly that they're their prior warning that there might be a delay in the <unk> date because of a delay in in conducting the facility inspection, but that is no longer an issue.

Ari Maizel: Have you started labeling discussions on that product yet? So, again, you know, we won't be commenting on the back and forth; however, the PDUFA date is still valid, which is April 30th, and typically, labeling discussions, just to give you a sense of the timing of the rhythm of NDA reviews, typically those occur approximately one month prior to the PDUFA date. Well, then maybe we can just flip to 05 and when, um... Follow your response exactly to FDA so we can know when those three months in your head, you know, when the clock started in your head. Hey, Mark, it's Mark.

Mhm have you started labeling discussions on that product yet.

So again, we won't be commenting on the back and forth.

However, the <unk> date is still.

<unk> is still valid so which is April 30th.

And and typically typically.

Tabling discussions just to give you a sense of timing of rhythm of NDA reviews, typically those occur at approximately one month prior to the <unk> date.

Mhm well.

And then maybe we can just flip to one five and <unk>.

When.

Did you follow your response exactly to FDA. So we can know when that three months in your head.

The clock started in your head.

Mark Jacobson: 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, And that is, you know... That's how we're thinking about the, I guess you could say, like, potential. Well, for planning purposes, like you said, not guidance, but for planning purposes, I think somewhere in there, if you add three months, but again, that's not guidance from us. That's just the potential range where something could occur.

Mark Hey, Mark its mark and so.

That was a.

Around year end and the first part of the year, what what we're tailoring to us.

When we received acknowledgement of receipt and confirmation of review and that's around the time, we 8-K that which I think it was like mid January .

And.

That is.

That's that's how we're thinking about.

I guess, you can say like potential.

Well for planning potential raising that guidance.

Pension arrangement I think somewhere in there if you had if you had three months okay.

But again, that's not a guidance from us that that's just potential range, where something could occur.

Sure.

Mark Jacobson: Right. So. Has there been any type of labeling negotiations on this product, or will you not comment on that either?

Right.

So.

Has there been any type of labeling negotiations on this product or were you not comment on that either.

Yeah.

So.

Mark Jacobson: 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 the lack of a PDUFA date, but with an ongoing review. So we do think that that would be something that is definitive.

So mark for excess or five 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 a lack of overdue.

But with an ongoing review so we do think that that that would be something that is definitive and and so currently.

Ari Maizel: And so currently, you could expect that once we have something definitive on that front, we would love 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?

You could expect that once we have something definitive on that front.

That we would we would look to.

Let the street know.

And something definitive would also be if you responded in the F. D. A basically came back and ask you a follow up question would that'd be definitive like has that happened yet.

Ari Maizel: They acknowledged your receipt, but have they actually asked you for anything else? Yeah, so Mark, what we've 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, you know, if you have not heard anything, then then, then there is nothing. Okay, and then, just completely different subject than 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.

They acknowledged you received but have they actually asked you for anything else.

Yeah, So omar.

Oh sure.

Yeah. So what we what we've said is is that we would let the street know once there was anything definitive in.

And that's clear from a from the FDA, we've been doing that and so you know if you have not heard anything then and.

And then there is nothing.

Right.

Okay, and then just completely different subject 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.

Amanda Jones: So, Kim's system, with our prior practice, will 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.

Sure so consistent with our prior practice, we will reveal the whole study design once we announced the launch of it but just to speak generally this study design will be similar to other registration trials for smoking cessation products.

Designs typically incorporate short treatment periods, followed by a treatment free observation period.

Okay.

Amanda Jones: [inaudible] And this is going to start when? We intend to provide further guidance on the initiation of a study within the year. Okay, thanks. Thank you. Our next question comes from Joseph Frome from Cohen & Company. Your line is now open, please go ahead.

And this is going to start with.

Yeah.

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

Okay. Thanks.

Okay.

Thank you.

Our next question from Joseph for them from Cowen and company.

Your line is now open. Please go ahead.

Joseph Frome: Good morning, and thank you for taking my questions. Maybe for the AXSO5 review, I know you highlighted the top line merit data to the FDA in the middle of last year. Have you provided any additional data to the agency on that trial? That's the first question that I would follow up on. So what 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. And then on the AXSO7 review... Are the analytical concerns that popped up with AXSR 5 applicable to AXSO 7? Did you have to make any changes there, or was that specific to AXSR 7?

Hi, there good morning, and thank you for taking my questions.

Maybe for the X So five review.

I know you highlighted the topline married data to the FDA.

Middle of last year have you provided any additional data to the agency on that trial and that's the first question that I have a follow up.

Yeah.

Yeah.

So what we did make me you have to be aware of.

The results of the study and and provided that information to the FDA and we have not made we have not.

<unk> provided any additional information apart from the results of the trial.

Okay.

And then on the access of seven review.

Are the analytical concerns that popped up in excess of five are applicable to an excess of seven did you have to make any changes there or is that specific to exercise.

Okay.

Ari Maizel: That was specific to AXS05, so, you know, we don't see any direct connection between the two. 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 of your disease and maybe..., would not have had an agitation relapse without treatment? Kind of how consistent is that? There's...

That was specific to our to access O five so.

So we don't see any direct.

Between the two.

Okay, Perfect and then maybe just last one on the Alzheimers agitation update I guess, how consistent our 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 youre going to have patients that have more severe disease and you know maybe just just wouldn't have had in agitation relapse without treatment and kind of how how consistent is easier.

There's.

Amanda Jones: There definitely is variability in the symptoms of the disease. So patients who are, 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 Quantum Mansfield Agitation Inventory has 29 items. So each of those items corresponds to a separate behavior.

There definitely is variability in the symptoms of the disease, so patients who are.

Amanda Jones: And so, those behaviors are clustered into different groups. So that reflects the variability in the presentation. Agitation can be manifested in different ways depending on the patient. Thank you. Our next question comes from the line of Matt Kaplan of Ladenburg and Felman. Your line is now open, please go ahead. Hi, good morning.

We have old timers disease, who are agitated. They may have they have a range of symptoms. So for example.

One of the common symptom scale to corn Mansfield agitation inventory has 29 items. So in each of those items corresponds to a separate behavior.

And so and in those behaviors and cluster in into different groups and so that reflects the variability in the presentation.

So agitation can be manifested in different ways depending on.

On the patient.

Thank you.

Okay.

Thank you.

Our next question comes from the line of Matt Kaplan of Ladenburg Thalmann. Your line is now open. Please go ahead.

Matthew Kaplan: 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.

Hi, good morning.

Just wanted to shift topics a little bit.

And maybe for Laurie can you talk a little bit about your commercial prep and specifically how your interactions have been going with with payers for and discussions are Oh, five and seven.

On the payer front.

Lori Englebert: Thanks. Thanks for the question. So, you know, as I stated in the prepared remarks, commercial prep for O5 is, you know, we are ready to go, and 07 is well on its way to tracking, tracking accordingly to, you know, potential. In terms of payer engagements for O5, we have been, we have engaged in permitted payer discussions since April of last year, and the amount of payers that we've engaged with, you know, in a permitted fashion covers almost the majority of So we've had great representation introducing Axsome as well as the clinical profile of O5, you know, to all the payers. Potential payers, making decisions.

Yeah, Hi, Matt. Thanks, Thanks for the question so.

As I stated in the prepared remarks commercial prep for O. Five as you know we are.

We are ready to go.

And Oh, seven is well on its way of tracking tracking accordingly to potential launch plan.

In terms of payer engagements.

Oh five we've been we are engaged in and permitted payer discussions since April of last year.

And the amount of payers that we've engaged with you know in our permitted fashion covers almost the majority of all commercial lives covered so so we've had great representation.

Introducing axiom as well as the clinical profile of a five you know to all of that.

The payers.

The potential payers and making decisions.

<unk>.

Lori Englebert: What I can tell you is that payers recognize that there is an unmet need for NDD, and they do recognize the novel mechanism of action associated with O5. And they're impressed by the Chronicle profile again, their 20 million NDD patients. Diagnosed right now, we see trends of that number, you know, continuing to increase. And we know that two-thirds do not achieve remission.

What I can tell you is that payers recognize that there is an unmet need.

Mbd and they do recognize the novel mechanism of action.

Associated with a five and they are impressed by the clinical profile again, you know there are 20 million M D patients.

Diagnosed right now we see trends of that number you know continuing to increase we know that two thirds do not achieve remission.

Lori Englebert: And the clinical profile for AXSO5 is extremely compelling, given the data package that we have with symptom reduction as early as one week and an achievement of remission. So we're encouraged by the discussions that we've had with payers. Dr. Ruffler not to tell any more.

And the clinical profile for <unk>.

Is extremely compelling.

The data package that we have with symptom reduction as early as one week and achievement of our mission at two weeks. So we're encouraged by the discussions that we've had.

With Payors and look.

Look forward to tell anymore once we get approval.

Lori Englebert: And then for XSO7, given the Phase 3 data which showed superiority to TRIPCAN, how do you think this will be utilized, and how will you position it in the market? Yeah, it's a great question. Thanks. So I'll, I'll, I'll answer a question you didn't really ask, although you did ask it in the last one.

Okay, and then for excess of seven because given the.

Phase III data, which which showed superiority to trip can I do you think this will be utilized and I guess and how are you positioned in the marketplace.

Lori Englebert: And that's around, you know, 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 cycle of patients.

Yeah. It's a great question. So I'll I'll I'll answer a question you didn't really ask although you did ask it in a last one and that's around you know 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.

Lori Englebert: To speak specifically to how we'll position ourselves within the HCP market, it's a bit premature to speculate on that right now, but we've continued to hone in on the fact that the accelerated absorption and the speed of action for our product will be meaningful to both HCP patients and doctors. Alright, thanks for taking the question. Thank you. The next question comes from Jason Gerberoy of Bank of America. Your line is now open; please go ahead. Hey, this is Perry on the line for Jason.

To speak specifically to have a position with in the S&P market, it's a bit premature to.

To speculate on that right now, but we continue to hone in on the fact that.

The accelerated absorption and the speed of action for our product is.

As will be meaningful to the ACP patients and Payors.

Alright, thanks for taking the question.

Thank you.

Our next question comes from Jason got the ROI of Bank of America.

Your line is now open. Please go ahead.

Hey, this is Perry on the one for Jason Thanks for taking our question.

Perry: Thanks for taking our question. Just a quick question on a chord, a crystal five. Attendee served tribal practice in the United States for 35 years. He wasombinoids. This has been based on, and I guess generally what the current enrollment is at at this time. I just want to get a sense of, you know, how

Just a quick question on accord extra so five Ah trial in the relapse rates could you could you tell us how many patients.

And this was this has been based on in and I guess generally what the.

Where the current enrollment is at at this time just wanted to get a sense of you know how.

Amanda Jones: A change in trial design, perhaps fewer patients seem to be enrolled. How that will impact the potential timeline of the trial. Thanks. Hi, yeah, so I'll start off before I'm turning it over to Amanda to answer the specific questions on the number of events and enrollment. But with regard to the timing of completion of the trial, we do not anticipate that that is going to change. So.

Yeah.

A change in trial design, perhaps less patient seems to be enrolled will how that'll impact.

The potential timeline for the trial.

Thanks.

Okay.

Hi, yes, so I'll I'll I'll start off before I was trying to get over to tremendous to answer specific questions on.

On number of events in enrollment.

But with regards to the timing of.

Completion of the trial, we do not anticipate that that is going to change too.

Amanda Jones: Sure, so based on just enrollment alone, we are on track four. The key thing that we're looking at is obviously 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. Thank you. Sorry, and just as a reminder, just to add to that, just remember that this is what we are referring to in the second part of the study, the randomized portion.

Yeah sure. So you know based on just enrollment alone we are on track for.

The plan readout.

You know mid next year or so the key thing that we're looking at is obviously you know when you 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 is.

What's kind of triggering our.

Desire for consultation with the FDA.

Got it thank.

Thank you.

Thank you and just as a reminder.

Sorry, and just as a reminder, just you start to add to that.

Just remember that that this is a we are referring to what's happening in the second part of the study the randomized portion.

Amanda Jones: All of these patients have previously received XSO5 and have been stabilized on XSO5 prior to randomization. Our next question... comes from Yatin Suneja of Guggenheim Securities. Your line is now open, please go ahead. Yeah, hi, this is Eddie on behalf of Yatin.

All of these patients had had previously received access of five and had been stabilized on excess so five prior to church randomization.

Okay.

Yeah.

Next question.

I'm from Yadkin Sunjata of Guggenheim Securities. Your line is all iPhone. Please go ahead.

Eddie: 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, like how should we think about 2022 revenues? How quickly can you penetrate this market?

Yeah, Hi, this is Eddie on for Gautam. Thanks for taking my question.

In terms of the label for <unk> five are there assumptions that you are 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 what's precluding those discussions and then assuming you can get an approval in the first half of the year like how should we think about 2012.

Two revenues how quickly can you penetrate this market and would you ever plan to provide revenue guidance and depression.

Ari Maizel: And would you ever plan to provide revenue guidance for depression? Thanks. Chowang, there are a lot of questions there, so before turning it to Lori to answer the question around assumptions with regard 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 regard to making you guys aware of that. And then, in terms of guidance for revenues for 2022.

So.

A lot of questions. There so before trying to get to to Lori to to answer the question around around assumption with regards to to the label in terms of on 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 so.

So that is our current thinking with regards to making you guys are aware of that.

And then in terms of guidance.

Lori Englebert: It's really premature for us to be providing revenue guidance on the product because the product is not yet approved. And also, we want to make sure that we understand what the label is, which leads us into the question that you asked with regard to labeling assumptions, and I'll turn that over to Lori. Lori Englebert Yeah, thanks for the question, Eddie.

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 to the question that you asked.

With regards to the labeling assumptions and I'll turn that over to Laurie yeah. Thanks for the question. So the best we can do in terms of commercial preparation as Ted Ted to prepare based off the label the draft label that you submit to.

Lori Englebert: So the best we can do in terms of commercial preparation is to make sure that we have the right label, Dr. Pierre, based on the label, the draft label that you submitted 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... Tweet me as fast as possible based on any labeling negotiations. Can you just remind us what that proposed label language is?

To the FDA, which obviously is highly substantiated from clinical trial results.

And so we are preparing for that I can't imagine that you know a major adjustments will be made to that label, but we are prepared to tweak as fast as possible based on any any labeling negotiations we get that.

Can you just remind us what that vote.

Proposed label languages.

Okay.

Lori Englebert: So what we've disclosed, as you know, is that the indication that we are going after is treatment for MDD. With regard to the specifics in the draft label, obviously, it would not be prudent for us to be disclosing that on a call. Thank you. Our next question comes from Ram Selvaraju of HD Wainwright. Your line is now open, please go ahead. Thanks very much for taking my questions. Firstly, just a quick clarification on the launch preparation timeline for both 05 and 07.

So when we bought it.

Disclose as you know is that the indication that we are going after is the treatment of <unk> with regards to the specifics and the draft label.

Obviously.

It would not be prudent for us to be disclosing that on a call.

Okay.

Okay.

Thank you.

Okay.

Thank you.

Our next question comes from Ram So for Q of H C. Wainwright. Your line is now I've Peng. Please go ahead.

Lori Englebert: Can you give us some additional clarity on assuming that 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 products? Oh, thanks, Ron, for the question. So, Lori, do you want to take that?

Thanks, very much for taking my questions. Firstly, just a quick clarification on the launch preparations timeline for both 0507 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 it to occur between the announcement of the approval and the actual commercial availability of product.

Okay.

Oh, Thanks, Rob for the question, Laura you want to take that yeah, So hey, Ron.

Ron: Yeah, so, hey, Ron, thanks for the question. So, you know, I think we previously discussed and disclosed that it will likely be within one quarter after approval, but that, in both cases, for both 05 and 07. Okay, secondly, on the smoking cessation front, just two additional points of clarification there that I was hoping you could provide. One is, in your 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...

Thanks for the question. So I think we've previously discussed and disclosed they will it will likely be with everyone corner after approval that we will launch.

And in both cases for both a five seven.

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.

In the discussion with the F D. A did they definitively indicate whether pop.

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.

Amanda Jones: Even in the context of positive top-line data from this study, a second confirmatory study would be necessary in smoking cessation. Um, so smoking cessation is a separate indication, and two positive trials are required. 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?

Even in the context of positive top line data from this study a second confirmatory study would be necessary in smoking cessation.

Hmm so.

Smoking cessation.

<unk> is a separate indication and two positive trials are required.

Okay.

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.

Amanda Jones: So given the product profile for XS05, 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 before. But no specific additional requirements or recommendations were provided by the agency beyond that.

So given the given the product profile for X S O five.

As you know because it has two API isn't it we do have to follow Ftes combination products rules and so we would have to demonstrate component contribution so one of the arms.

Would likely have to be a b program.

Yeah.

But no specific additional requirements or.

Recommendations were provided by the agency beyond that is that correct.

Amanda Jones: Is that correct? Well, Ram, as Amanda mentioned earlier, 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, we'll be able to provide you with details. We don't like to speculate prior to launching a study because, you know, as you know, the design can change.

Well Rob.

I think is 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.

To finalizing the study design and and then once we once we launch it.

We'll be able to provide you details we don't like to speculate prior to launching a study because as you know but design can change.

Amanda Jones: And then the last question is, with respect to the Narkolepsy 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, Ram, I'll turn that over to Amanda to comment on that.

Understood and then 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 our Serrano I'll turn it over to traumatic to comment on that.

Amanda Jones: Sure, thanks. So, yes, you know, if the Symphony study has positive results, then that would be, you know, the basis of efficacy for our NDA. We do also have an ongoing open-label study as well, and that study is anticipated to complete approximately six months after this study. Thank you. Our next question comes from Vikram Purohit of Morgan Stanley. Your line is now open, please go ahead. Good morning, everyone. This is Gaspo on behalf of Vikram.

Sure thing so yes.

If the Symphony study has positive results then that would be the basis for our NDA. We do also have an ongoing open label study as well.

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 fit quiet a bit from Paul Rohit <unk> of Morgan Stanley . Your line is my wife Peng. Please go ahead.

Amanda Jones: Thanks for taking our question. I was wondering if you could walk us through how the BCC platform works, what the metrics are that you have been testing against, and how you will monitor its utility in a real world setting.

Good morning, everyone. This is gospel unfold vikram, thanks for taking our question.

Was wondering if you could.

Walk us through how do you see platform works what the metrics are that you have been testing I guess on how you would monitor.

And the real world setting.

Yeah go ahead Yep Yep Yeah. Please.

Gaspo: Yeah, yeah, yeah, please. I think that's a question for Lori. Yeah, if you'd like to answer that, go ahead. No, please, no.

I think that's a question for Laurie if you like to answer that go ahead.

[laughter] right. We're very excited here you can tell we're arguing over who is going to answer the question.

Lori Englebert: 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'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. 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 Axsome touchpoint, whether that be with reps to HCPs or patients.

Thanks for the thanks for the question. So first of all let me let me just start out with with why why we were excited about about D. C C.

Fundamentally we believe that.

The goal of any engagement with an ACP or patient is that it's meaningful and impactful and in order to achieve that what we did was designed.

A technology enabled platform that uses AI machine learning.

Sophisticated data and analytics really to synthesize data points that are collected and then deploy that to any axiom touch points, whether that be with reps to hep's.

Or for patients.

Lori Englebert: And the way that we came about, you know, developing this platform is that we did fairly extensive research into 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, but it is now seamlessly integrated.

And the way that we came about developing this platform is that we did you know 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 with several different systems too that it is now seamlessly integrated.

Lori Englebert: In terms of KPIs and metrics and what we're planning for. Because we believe that meaningful engagements 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.

In terms of Kpis and metrics and what we're planning for them, 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.

Lori Englebert: 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 trying. 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 randomized into the withdrawal portion is and also how you're classifying relapse?

When we get close to approval are once we have approval and we start discussing.

<unk> size I can give you more details around the additional metrics that will well be tracking.

Okay.

Thank you.

Our next question comes from the line of Myles Minter off.

William Blair. Your line is now open. Please go ahead.

Lori Englebert: 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.

Hi, Thanks for taking the questions just on the accord study from zero to five.

Have you disclosed what the definition of response to be randomized into the withdrawal portion is and also how you're classifying very lapse I know in advance you used collyn Mansfield I was just wondering whether it's different chill and whether or not a very stringent relapsed criteria on that scale.

What's driving the event right less than what you had predicted.

Myles Minter: Sure, Amanda. Sure. Thanks for the question. So, you know, the response rate, 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 standard measures of Alzheimer's disease agitation, so similar to some other programs that are ongoing. Okay, so, but the relapse... Is it safe to say that it is the common man's field, or is it just like an event of agitation? 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.

Sure sure.

Sure. Thanks for the question so the.

The response rate, we will disclose that when you know.

When we released the topline results of the study.

We do want to make note that yeah. The study does include standard measures of Alzheimer's disease agitation. So similar with some of the programs that are ongoing.

Okay sorry.

The relapse measurement.

Is it type decided that it is Colin Mansfield or is it just like an event of agitation.

Yeah.

Yeah.

Yes. So there is a formal definition, which is driven by data driven.

A definition.

We're just we'll be releasing the full formal definition.

The later date.

Amanda Jones: 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.

Okay Cool and then I did not as obviously, it's all under.

The review and you've Gotta go talk to the FDA, but you are reiterating first half 'twenty three guidance in the press release I was just wondering why that is and I gather you're messaging that we expect that to change but.

Maybe just to the point of what we don't know when that is changing too. So we just won't change it yet I'm just curious as to why you guys stated that rather than withdrawing plumbing got it and see it.

Herriot Tabuteau: And I gather your messaging that we expect that to change, but maybe just for the point of, we don't know when that's changing, so we just won't change it yet. I'm just curious as to why you've stated that rather than withdrawing time and guidance here. Yeah, so I think the reason for that is that in giving our prior guidance, we did try to incorporate some buffer. And so currently, you know, we don't see any reason to change that guidance, but we did want to alert folks to the fact that there may be, 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.

Yeah. So.

I think the reason for that is isn't giving our prior guidance. We did tried to incorporate some buffer.

And and so currently we don't see any reason to change that guidance, but we.

We did want to alert folks too to the fact that.

There may be it may change and that it is an active process and we.

Do you want to take advantage of the fact that we have this dialogue with the FDA, we want to make sure that the study design as appropriate but for.

Herriot Tabuteau: But for now, in terms of guidance, you know, we don't see any reason yet to formally change it. We will be coming back to you guys and providing an update, you know, as appropriate. But until then, our guidance is our choice. I think that's all. We'll see you next time. Bye. Bye. 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. Just had a question on, Unknown Attendee, Ashwani Verma, Ari Maizel, Axsome. Unknown Attendee, Ashwani Verma, Ari. Yeah, hi, David.

So 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.

This is our guidance.

Uh huh.

Cool thanks for the questions.

Right.

Thank you. Our final question comes from the line of David talk after.

F N B C Yolanda Salt life Peng. Please go ahead.

Hey, guys. Thanks for fitting me in here.

Just had a question on the B.

The sales force or are launching.

Launching five M. D. D can you just remind us of.

The sales force numbers that you would expect are necessary to successfully support.

The launch an M. D E. And then you know how are you sort of managing expectations. There with contingent offers given given the unusual situation with the <unk>.

<unk> review.

Yes.

David Hogg: Thanks. 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, you know, that equates to roughly 23,000 HCPs in the NDD. Well, you know, we will reveal Salesforce size the closer we get to approval. [inaudible] In terms of the contingent offers, I couldn't be more proud of the field leadership that we have out in the field. Just to give you a statistic that the field leadership that we hired in the field was operating on a less than 1% acceptance rate of applications to positions. So we have the best of the best.

Yes, Hi, David Thanks. Thanks for the question. So we are 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 the high prescribing physicians out there and that that equates to roughly 23000, hcp's and empty space.

Well rewarded with Vale Salesforce size, the closer we get to approval and launch.

In terms of the contingent offers.

Couldn't be more proud of the sales leadership that we have out in the field.

We are.

Just to give you.

Ethics that the field leadership that we hired in the field.

We're operating on a less than 1% acceptance rate of our.

Applications to physicians.

So we have the best of the best.

Lori Englebert: 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 pipeline.

What they've done over the past.

Several months, where the extended delay Israeli not only to build their team, but also to to keep them highly engaged and excited about the opportunity.

Okay. Thanks, so much for taking the question.

Yeah.

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

Okay.

Lori Englebert: 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 bringing 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. Thank you.

Well. Thank you all for joining us again on the call today 2022.

He is a potentially pivotal year for Exxon with the potential for two new product approvals for depression in migraine.

And also the continued advancement of the rest of our industry, leading CNS pipeline. So all in all we have for 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.

Look forward to keeping you updated on our continued progress throughout the year and have a great day.

Yeah.

Yeah.

This concludes today's conference call you May now disconnect your line.

Okay.

Uh huh.

Uh huh.

Herriot Tabuteau: 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 of iteration. And so, we do watch the event rate carefully. And also, typically, the way that those parameters are set out prospectively is that they're based on prior information with a particular indication. In the case of Alzheimer's disease agitation, there currently is no product that is approved.