Q3 2021 Axsome Therapeutics Inc Earnings Call

Good day, and thank you for standing by welcome to the at some third corner a 2021 financial results conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your telephone.

Operator: and Thank you for standing by. Welcome to the Axsome third quarter 2021 financial results conference call.

Operator: At this time, all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you need to press star one on your telephone. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Mark Jacobson, Chief Operating Officer. Please go ahead. Thank you, operator. Good morning. And thank you all for joining us on today's conference call.

If you require any further assistance. Please press star zero I would now like to hand, the conference over to your Speaker today, Mark Jacobson Chief Operating Officer. Please go ahead.

Thank you operator, good morning, and thank you all for joining US on today's conference call. Our earnings press release, providing a corporate update and details of the company's financial results for the third quarter of 2021 crossed the wire a short time ago and is available on our website at <unk> Dot com.

Operator: Our earnings press release providing a corporate update and details on the company's financial results for the third quarter of 2021 crossed the wire a short time ago and is available on our website at axome.com. During today's call, we will be making certain forward-looking statements. These statements may include, but are not limited to, statements...

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 anti itch.

Mark L. Jacobson: Regarding, among other things, the efficacy,

Mark L. Jacobson: [inaudible] 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. These and other risks are described in our periodic filings with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these four listed statements, which are only made as of today.

Debated 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 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.

Mark L. Jacobson: 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; Dr. Kevin Laliberte, Executive Vice President, Product Strategy; Lori Englebert, Senior Vice President of Commercial and Business Development; and Dr. Amanda Jones, Senior Vice President of Critical Development. Ariel will first provide an overview of the company and then review recent developments and upcoming milestones.

<unk> disclaims any obligation to update such statements.

Joining me on the call today are Dr area attributes, So chief Executive Officer, Nick PV, Chief Financial Officer, Dr. Kevin Liberty Executive Vice President product strategy, Laurie Inglebert Senior Vice President of commercial and business development and Dr. Amanda Jones Senior Vice President of clinical development.

Area 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.

Mark L. Jacobson: Following Ariel, Lori will provide a commercial update.

Mark L. Jacobson: And then Nick will review our financial results. We will then open the line for questions.

We will then open the line for questions.

Mark L. Jacobson: Questions will be taken in the order they are received. And with that, I will end the call.

Questions will be taken in the order they are received.

With that I will turn the call over to Ariel.

Mark L. Jacobson: I turn the call over to Ariel.

Ariel: Thank you, Mark. Good morning, everyone, and thank you all for joining Axsome Therapeutics' third quarter 2021 financial results and business update conference call. Over the past several months, we have continued to advance our differentiated, late-stage CNS product candidates aimed at meaningfully improving the lives of patients. I will provide an update on our development pipeline before turning it to Lori, who will provide a commercial update.

Thank you Mark good morning, everyone and thank you all for joining axon Therapeutics third quarter 2021 financial results and business update conference call over.

Over the past several months, we have continued to advance our differentiated late stage CNS product candidates aimed at meaningfully improving the lives of patients.

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

Ariel: Starting with our first lead product candidate, AXSO5, which is undergoing an NDE review for the treatment of major depressive disorder. The FDA did not take action on the NDA by the August 22nd PDUFA date, as previously disclosed, and the review of the application is ongoing. The Agency recently informed us of two deficiencies related to analytical methods in the Chemistry, Manufacturing, and Control section of the NDA that must be addressed prior to the FDA taking action on the NDA.

Starting with our first lead product candidate <unk>.

So five which is undergoing an NDA review for the treatment of major depressive disorder.

The FDA did not take action on the NDA by the August 22nd but do predict that.

Previously disclosed and review of the application is ongoing.

The agency recently informed us of two deficiencies related to analytical methods and the chemistry manufacturing and controls section of the NDA, which must be addressed prior to the FDA taking action on the NDA. We believe these deficiencies are addressable and or confirming the details of the request with the FDA.

Ariel: We believe these deficiencies are addressable and are confirming the details of the request with 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 based on current enrollment trends, we anticipate completion of the trial in the first half of 2023. With regard to the development of AXSO5 in smoking cessation, we received positive pre-IND meeting written guidance from the FDA on a proposed clinical development plan.

Yeah.

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

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

And based on current enrollment trends, we anticipate completion of the trial in the first half of 2023.

With regards to the development of the excess so five in smoking cessation, we received a positive pre IMD meeting written guidance from the FDA on it.

Post clinical development plan.

Ariel: Based on this feedback, we plan to proceed to a pivotal Phase 2-3 trial in this indication and expect to provide timing for initiation of that trial next year. Moving on to our second lead product candidate, AXS07, a multi-mechanistic acute treatment for migraine. The NDA for AXS 07 was accepted for review by the FDA with a PDUFA target action date of April 30, 2022. However, the FDA has also informed us that due to COVID-19 pandemic-related travel restrictions, they may be unable to complete an inspection of one of the AXS07 manufacturing facilities prior to the PDUFA date. They will continue to monitor the public health situation, as well as travel restrictions, and we will keep you informed of any developments on this front.

Based on this feedback we plan to proceed tweet pivotal phase two three trial in this indication and expect to provide timing when initiation of that trial next year.

Moving on to our second lead product candidate, except for seven multi mechanistic acute treatment for migraine.

The NDA for excess so seven was accepted for review by the FDA with a put do foot target action date of April 30 of 2022.

The FDA has also informed us that due to COVID-19 pandemic related travel restrictions they may be unable to complete an inspection of one of the excess so seven manufacturing facilities prior to the <unk> date.

They will continue to monitor the public health situation as well as travel restrictions and we will keep you informed of any developments on this front.

With two NDA is under active review exome is in a position to potentially commercialize two new treatments in the near to intermediate term for patients living with depression and migraine.

Ariel: With two NDAs under active review, Axsome is in a position to potentially commercialize two new treatments in the near to intermediate term for patients living with depression and migraine. Lori will provide details on our commercial launch readiness for AXSO5, and our pre-launch commercial activities for AXS 07. The rest of our rich pipeline continues to advance. For AXS12, our product candidate being developed for the treatment of narcolepsy, we initiated a symphony phase 3 trial in the third quarter.

Lori will provide details on our commercial launch readiness for a successful five.

Our prelaunch commercial activities for access so seven.

The rest of our rich pipeline continues to advance.

For your excess 12 hour product candidate being developed for the treatment of narcolepsy, we initiated a symphony phase III trial in the third quarter.

Ariel: Enrollment in the 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. Based on the status of these activities, we now expect to submit the NDA in 2023. I will now turn the call over to Lori, who will provide a commercial update. Thank you, Ariel, and good morning.

Coleman and the trial is progressing and top line results are anticipated in the first half of 2023.

Well the excess 14 product candidate for the treatment of fibromyalgia manufacturing and other activities related to the planned submission of an NDA are ongoing.

Based on the status of these activities, we now expect to submit the NDA in 2023.

I will now turn the call over to Laurie who will provide a commercial update.

Thank you Ariel and good morning.

Lori Englebert: Today, I will give you an update on our commercial activities as it relates to launch readiness for AXS 05 and pre-launch activities that are progressing for AXS 07. As Ari has stated, the commercial team has been actively preparing for the potential launch of AXSO5, and we remain incredibly excited about the opportunity to bring this product to market for the millions of patients suffering from depression. We are ready and prepared should we receive approval.

Today, I will give you an update on our commercial activity as it relates to launch readiness for access of five and prelaunch activities that are progressing for access outside of it.

As Eric stated the commercial team has been actively preparing for the potential launch that's right and we remain incredibly excited about the opportunity to bring this product to market for the millions of patients suffering from depression.

We are ready.

[noise] prepared should we receive approval.

Lori Englebert: The U.S. remains in the middle of a mental health crisis. Multiple studies have been released recently stating dramatic increases in depression due to the COVID-19 pandemic. Most recently, a global study published in the Lancet showed that worldwide rates of depression climbed by 28% in 2020, showcasing the devastating ripple effect of the COVID-19 pandemic. Awareness of mental health issues is at an all-time high, and people are talking about mental health today more than ever.

The U S remains in the middle of a mental health crisis multiple studies have been released recently, stating dramatic increases in depression due to the COVID-19 pandemic.

Most recently a global study published in Lancet showed that worldwide rates of depression climbed by 28% in 2020, showcasing a devastating ripple effect of the COVID-19 pandemic.

Awareness of mental health issues is that an all time high and people are talking about mental health today more than ever.

Lori Englebert: Given the personal and economic burden associated with mental health conditions, there is an undeniably urgent need to bring support to those affected. If approved, AXSO5 would be an important new treatment option for the many Americans living with depression. We are prepared and ready to bring this meaningful innovation to patients by commercializing the product soon after potential approval. Our commercial launch strategy is innovative and purposeful, with the intent to bring important new products to market in a meaningful way. We have undertaken great efforts to understand the needs of patients and the health care professionals who treat them.

Given the personal and economic burden associated with mental health conditions, there isn't undeniably urgent need to bring support it does affect it.

If approved <unk>.

Oh, five would be an important new treatment option for the many Americans living with depression.

We are prepared and ready to bring this meaningful innovation to patients by commercializing the product soon after potential approval.

Our commercial launch strategy and innovative and purposeful with the intent to bring important new products to market in a meaningful way.

Have undertaken great effort to understand the needs of patients and to health care professionals, who treat them.

Formation has informed our strategy.

Our digital centric commercialization or D. C. C technology enabled platform designed to increase efficiency and effectiveness of our marketing effort is fully implemented tested and ready for execution.

Lori Englebert: This information has informed our strategy, our digital-centric commercialization.

Lori Englebert: or DCC technology-enabled platform designed to increase the efficiency and effectiveness of our marketing efforts is fully implemented, tested, and ready for execution. As a reminder, we have designed our DCC platform to use streamlined systems and digital enablement tools, combined with sophisticated data and analytics to allow for a more effective, efficient, and meaningful

As a reminder, we have designed our D. C C platform 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.

Last quarter I stated that our impressive field leadership team is fully staffed.

Over the past several months they have been working hard on recruiting top talent to staff our sales representative positions.

At this time, we have offers formulary acceptance break complete salesforce team.

Lori Englebert: in Meaningful Engagement with Physicians and Patients

Lori Englebert: Last quarter, I stated that our impressive field leadership team was fully staffed. Over the past several months, they have been working hard on recruiting top talent to staff our field representative positions. At this time, we have offers formally accepted for a complete Field Force team. All offers are contingent upon approval.

All offers are contingent upon approval.

In the event of a potential approval, we anticipate having all field representatives onboard trained and certified by launch.

Our highly capable and experienced market access team continues to engage with payers and ongoing permitted discussions ensuring awareness of axiom, our pipeline and the clinical profile. Okay. That's fine.

We look forward to engaging with payers immediately after approval.

Yeah.

Our marketing and patient support services teams have been working hard to ensure that our comprehensive patient support services.

Lori Englebert: In the event of a potential approval, we anticipate having all field representatives on board, trained, and certified by launch. Our highly capable and experienced market access team continues to engage with payers in ongoing, permitted discussions, ensuring awareness of Axsome, our pipeline, and the clinical profile of AXSO5. We look forward to engaging with payers immediately after approval. Our marketing and patient support services teams have been working hard to ensure that our comprehensive patient support services and all marketing materials are complete, implemented, and ready for execution in anticipation of a potential approval.

And all marketing materials are complete implemented and ready for execution in anticipation of a potential approval.

Our launch readiness preparations have been heavily focused on access on five.

However, we are also actively preparing for a potential subsequent march seven.

<unk> for the acute treatment of migraine.

Debilitating disease and continues to have a tremendous unmet need and impact an estimated 37 million U S. Adults.

Marketing activities are well underway, along with D. C C integration and initiating exercise seven permitted payer discussions.

We are enthusiastic about the potential opportunity that accepts or seven could bring to a market. That's still seats close to a 70 per cent dissatisfaction rate with currently available therapies.

Lori Englebert: Our launch readiness preparations have been heavily focused on AXSO5. However, we are also actively preparing for a potential subsequent launch of XSO7 for the acute treatment of migraine, a debilitating disease that continues to have a tremendous unmet need and impacts an estimated 80% of the global population.

The differentiated clinical profiles for both excess of five and seven have the potential to bring significant benefit to patients and the physicians who treat them.

We are excited about the opportunity for potentially bringing these important new products to market in an innovative and meaningful way.

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 third quarter 2021 results and provide some financial guidance. We ended the third quarter with approximately $115 million in cash compared to roughly $141 million at the end of the second quarter, a net decrease of approximately $26 million.

Lori Englebert: impacts an estimated 37 million U.S. adults

Lori Englebert: Marketing activities are well underway, along with DCC integration and initiating AXA's

Lori Englebert: Permitted Payer Discussion

Lori Englebert: We are enthusiastic about the potential opportunity that AXSO7 could bring to a market that still sees close to a 70% dissatisfaction rate with currently available therapies. The differentiated clinical profiles of both AXS 05 and AXS 07 have the potential to bring significant

R&D expenses were $13 $2 million for the quarter, ending September 32021 versus $14 8 million for the comparable period in 2020.

The decrease in R&D expense was driven by the completion of the NDA, enabling clinical trials that were ongoing in the prior comparable period.

G&A expenses were $20 2 million for the quarter ending September 30 of 2021 at $6 3 million for the comparable period in 2020. The increase was primarily related to pre commercial activities and personnel expense along with an increase in noncash stock compensation expense.

Lori Englebert: We are excited to announce that we are offering Significant Benefits to patients and the physicians who treat them.

Lori Englebert: We are excited about the opportunity to potentially bring these important new products to market in an innovative and meaningful way.

Net loss was $34 9 million or <unk> 93 per share for the quarter ended September 32021, compared to a net loss of $22 9 million or 61 cents per share for the comparable period in 2020.

Nick Pizzie: I will now turn it over to Nick, who will review our financials.

Nick Pizzie: Thank you, Lori, and good morning, everyone. Today, we'll discuss our third quarter 2021 results and provide some financial guidance. We ended the third quarter with approximately $115 million in cash compared to roughly $141 million at the end of the second quarter, a net decrease of approximately $26 million. R&D expenses were $13.2 million for the quarter ending September 30, 2021, versus $14.8 million for the comparable period in 2020. The decrease in R&D expenses was driven by the completion of NDA-enabling clinical trials that were ongoing in the prior comparable period.

We recently announced that we have expanded our term loan facility with Hercules capital to $300 million with $100 million now available upon FDA approval of excess so five and M. P D and access to an additional $150 million thereafter this.

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

We believe our current cash position of $115 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 at least 2020 for.

Nick Pizzie: G&A expenses were $20.2 million for the quarter ending September 30, 2021, and $6.3 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. The net loss was $34.9 million, or $0.93 per share, for the quarter ended September 30, 2021, compared to a net loss of $22.9 million, or $0.61 per share, for the comparable period in 2020.

That concludes our third quarter 2021 financial review.

I'll turn the call back to Mark to lead the Q&A discussion.

Operator may we please have our first question.

At this time to ask a question press Star then the number one on your telephone keypad. Your first question comes from Charles Duncan of Cantor Fitzgerald.

Yeah.

Good morning.

Thanks, Ariel and team for the update and for taking our question.

Yeah, so regarding access O five and the analytical deficiencies that were mentioned.

So I'm wondering if you could provide us a little bit more color. If you will on that in terms of what would be expected to.

Nick Pizzie: We recently announced that we have expanded our term loan facility with Hercules Capital to $300 million, with $100 million now available upon FDA approval of AXS05 and MVD, and access to an additional $150 million thereafter. This committed, non-diluted capital gives us additional financial flexibility through both anticipated potential commercial launches for AXS05 and AXS07. We believe our current cash position of $115 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 at least 2024.

To be able to address the deficiencies are there any additional clinical.

Or non clinical experiments that you need to run or do you think that you'll be able to address these with information that you have on hand.

And if so what kind of timing are we are we looking at is it months or quarters.

Thanks, Charles for the question I'll turn it over to to Kevin to answer that question.

Great. Thanks for the question. So just just to give an update.

We are actively working on the update to the analytical method that the FDA has requested.

But we are still in communication with the FDA to fully understand the specifics and in the process to resolve.

The items that they brought to our attention I will note that they are manufacturing specific that we understand right now so.

Mark L. Jacobson: That concludes our third quarter 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? At this time, to ask a question, press star, then the number one on your keypad.

So it would be solely resolved from a manufacturing point of view based on what we understand from the agency at this time.

And we.

We expect our work to be complete on those methods in the in the near to intermediate term for resolution.

Okay. That's helpful. So you don't anticipate it impacting any ongoing studies with our product candidate.

Charles Cliff Duncan: Your first question comes from Charles Duncan of Cantor Fitch. Yeah, good morning. Thanks, Ariel and team, for the update and for taking our question. Yeah, so regarding AXS 05 and the analytical deficiencies that were mentioned, I guess I'm wondering if you could provide us with a little bit more color, if you will, on that in terms of what would be expected to address the deficiencies. Are there any additional clinical or non-clinical experiments that you need to run? Or do you think that you'll be able to address these with the information that you have on hand? And if so, what kind of timing are we looking at? Is it months or quarters?

We would not anticipate that that that.

That would have an impact on any ongoing studies.

Okay Super and then my second question is maybe for aerial or someone on the team to wax philosophical philosophically about the treatment landscape in M. D. D. Lorie mentioned the challenges of mental health and how awareness is real.

Really increased and lots of discussion on that but I guess I'm wondering when do you think about daily chronic therapy paradigm of historic.

Kevin: Thanks, Charles, for the question. I'll turn it over to Kevin. Great. Thanks for the question. So just to give an update, we are actively working on the update to the analytical methods that the FDA has requested, but we are still in communication with the FDA to fully understand the specifics and the process to resolve the items that they brought to our attention. I will note that they are manufacturing-specific as we understand right now, so they would be solely resolved from a manufacturing point of view based on what we understand from the agency at this time. And we expect our work to be complete on those methods in the near to intermediate term for resolution.

Versus say, an intermittent treatment paradigm certainly for the more highly burdened patient how do you think about that relative to access Oh, five and its role in the in the future treatment landscape.

Yeah.

We're excited about the potential role of yeah can survive in the treatment landscape because you know that the current treatment landscape leaves the vast majority of patients.

With inadequate responses that is in terms of not just clinical response.

The reduction of 50% of symptoms, but also of remission.

Kevin: Okay, that's helpful. So you don't anticipate it impacting any ongoing studies with product candidates?

And and if you look at those parameters in the studies that we have conducted with it because of the five and those have been multiple studies now are well controlled as well as open label in various patient populations.

Kevin: We would not anticipate that that would have an impact on any ongoing studies. Okay, good.

The product are definitely shows that it could meaningfully.

<unk> impact.

Ariel: And then my second question is maybe for Ariel or someone on the team to wax philosophically about the treatment landscape for MDD. Lori mentioned the challenges of mental health and how awareness has really increased, and there was lots of discussion about that. But I guess I'm wondering when you think about the daily chronic therapy paradigm of historic versus, say, an intermittent treatment paradigm certainly for the more highly burdened patients, how do you think about that relative to AXS-05 and its role in the future treatment landscape?

The the treatment landscape and reduce rates of Oh depression, and improved rates of remission as well as a clinical response. So we're really excited about that and.

As a reminder, the the.

Breadth of of the types of patients that we studied spans the gamut from totally naive patients who've never been treated with an anti depressant to patients with treatment resistant depression, who have had multiple lines of treatment and the product so for appears to perform.

Equally well in all of those lines of treatment. So.

The other aspect to them.

Ariel: We're excited about the potential role of XSO5 in the treatment landscape because, as you know, the current treatment landscape leaves the vast majority of patients with inadequate responses. That is in terms of not just clinical response, meaning the reduction of 50% of symptoms, but also of remission, and if you look at those parameters in the studies that we have conducted with the XSO5, and those have been multiple studies now, both controlled as well as open label in various patient populations, the product definitely shows that it could meaningfully impact.

Which is notable as the new mechanism of action, which we think is contributing to the clinical benefit that.

That we're seeing and so we're as a company, we're really excited to be developing a product, which not only is needed by a large percentage of them.

Population.

But which is timely given the impact of the mental health pandemic.

On being presented in some depression.

Laurie do you have anything to add to that.

I'm sure Charles I always love waxing poetic, but I'm, what I'm about the state of Israeli based off of.

An extensive amount of discussions when they see pes and market research that we performed there is undeniably an undeniable need for a rapid onset of action in these patients, but you know what.

Ariel: We're really excited about that, and as a reminder, the breadth of the types of patients that we have studied spans the gamut from totally naive patients who've never been treated with an antidepressant to patients with treatment-resistant depression who have had multiple lines of treatment. And the product so far appears to perform equally well in all of those lines of treatment. The other aspect, which is notable, is the new mechanism of action, which we think is contributing to the clinical benefit that we're seeing.

I think people should not lose sight of is that only gets you a little bit of the way what physicians are really concerned about is remission and durability and and you know the durability piece given that and our product has shown durability based off several studies.

We believe we'll put will bode well for us.

Very good thanks for the added color look forward to the update on the analytical message.

Yeah.

Your next question comes from Joseph Thome, with Cowen and company.

Hi, there good morning, and thank you for taking my questions. Maybe the first one on the deficiencies are these the only deficiencies that spurred the earlier letter or were there other deficiencies that you have since resolved with the FDA that you're aware of.

Ariel: And so, you know, we're, as a company, really excited to be developing a product that is not only needed by a large percentage of the population but which is timely, given the impact of the mental health pandemic on the increased incidence of depression. Lori, do you have anything to add to that? Sure, Charles, I always love Waxing Poetic, but what I'm about to state is really based on an extensive amount of...

And then maybe second just on the the Merit T. R D data.

Should are because if I'd be approved and launched how can you best leverage some of these.

Resistant and refractory patient datasets given that the label is going to be for empty. Thank you.

Lori Englebert: Discussions with HEPs and market research that we perform. There is an undeniable need for a rapid onset of action in these patients, but what I think people should not lose sight of is that that only gets you a little bit of the way. What physicians are really concerned about is remission and durability, and the durability piece, given that our product has shown durability based on several studies, we believe will bode well. Very well. Thanks for the added color.

Thanks, Thanks for the question Joseph a.

With regards to our the the deficiencies that we disclosed today. These are the only deficiencies that we haven't been made but we haven't been made aware of them. So.

We're working with the FDA, obviously as we've stated.

As stated to get clarity on the exact response.

This does not mean that these are the only deficiencies war only pieces of information that the FDA will request during the review there could be more or these could be the only ones. So just just to be clear. So we're not making any predictions.

Charles Cliff Duncan: I look forward to the update on the analytical methods. Good day. Your next question comes from Joseph Doan with Cohen & Company. Hi there, good morning, and thank you for taking our questions. Maybe the first one on the deficiencies: are these the only deficiencies that spurred the earlier letter, or were there other deficiencies that you have since resolved with the FDA that you're aware of? And then maybe second, just on the merit TRD data. Should AXSFI be approved and launched, how can you best leverage some of these resistant and refractory patient data sets given that the label is going to be for MDD? Thank you.

And with regards to the to your D data that we've generated and not just in the Merit study but.

You know the clinical trials that we've conducted.

To be clear you know the indication that we have applied for and that we are currently under review for <unk> is M. D. D. That's the indication on the additional data that we've generated we think will inform.

Physicians.

Other health care professionals, because they do see you know.

All sorts of patients all kinds of patients will come to them and and it will be up to them to you know to make up their mind as to how best to treat their patients. So you know we were trying to answer a practical questions with regards to you know once the product.

Joseph John: Thanks for the question, Joseph. With regard to the deficiencies that we've disclosed today, these are the only deficiencies that we have been made aware of. We're working with the FDA, obviously, as we've stated, to get clarity on the exact response. But this does not mean that these are the only deficiencies or only pieces of information that the FDA will request during the review. There could be more, or these could be the only ones.

Is available and how it may perform them, but to be clear the indication that we are focused on is Ah indication, which is nice broad it doesn't Congress.

The.

The full breadth of patients with that with M D.

Great. Thank you.

Your next question comes from for meal Divan with Mizuho Securities.

Great. Thanks, so much for the call and for taking my questions, maybe one more just around the.

Deficiencies that the FDA mentioned can you clarify just sort of when you found out about diesel I guess.

Joseph John: Just to be clear, we're not making any predictions. And with regard to the TRD data that we've generated, not just in the merit study but in other clinical trials that we have conducted, let's be clear, you know, the indication that we have applied for and that we are currently under review for is MDD. And so that's the indication. The additional data that we've generated, we think, will inform physicians and other healthcare professionals because they do see all sorts of patients, all kinds of patients who will come to them, and it will be up to them to, you know, make up their minds as to, you know, how best to treat their patients.

It just seems like an unusual process here that you're going through as opposed to maybe getting a foremost PRL in responding to that the way. Other companies have do you have any insights just I don't know.

Maybe it's more of a question for the FDA, but I'm wondering if there's anything you can share them.

Why you Sir ended up into sort of unusual.

No path here and then the second question.

I had was more on the agitation trial and it looks like you.

Just kind of shifted out the timing for when that's going to be completed by a little bit I'm. Just curious if you can give an update on exactly how far you are into enrollment in that trial at this point and anything that sort of has changed in terms of why the timing wise thing a little bit longer to complete than than you previously thought.

Joseph John: So we're trying to answer a practical question with regard to once the product is available and how it may perform. But to be clear, the indication that we are focused on is the NDD indication, which is nice. It is broad. It does encompass. Great, thank you. Your next question comes from Vamil Devan with Mizzou Health Securities.

<unk>.

Thanks Shlomo for the questions.

I'll turn the agitation.

Question over to.

Over to Amanda <unk>, who will provide some color on the trial.

Maybe some of the unique aspects of the trial and and and how that would impact our interpreting enrollment trends, there, but a bit but I'll start by first answering your other questions in terms of the timing of when we Oh.

Got the communication from the FDA on these deficiencies. We recently got them. So very end of October and since then.

Vamil Devan: Great, thanks so much for the call and for taking my questions. Maybe one more just around the deficiencies that the FDA mentioned.

We've been.

I'm trying to get details on them. So that we could specifically respond. So we're still in the process of getting those of those details.

Vamil Devan: Can you clarify just sort of when you found out about them? And I guess it just seems like an unusual process here that you're going through, as opposed to maybe being a formal CRL and responding to that the way other companies have. Do you have any insights? Just I don't know, maybe it's more of a question for the FDA.

And in terms of in terms of.

What you term.

Characterizes the unusual nature of this process.

It is a unique situation, but but remember this is actually not unusual to receive.

Information requests from the FDA during NDA review, where they might ask for additional information you know whether that'd be.

Vamil Devan: But I'm wondering if you can share why you sort of ended up on this sort of unusual path here. And then the second question I had was more about the agitation trial. And it looks like you just kind of shifted the timing for when that's going to be completed by a little bit. I'm just curious if you can give an update on exactly how far you are into enrollment in that trial at this point, and anything that sort of has changed in terms of why the timing, why it's taking a little bit longer to complete than you previously thought. Thank you.

And in any discipline and including CMC as we have received so we don't view.

We don't want to use this information requests from the F D a as as unusual in and of itself.

So I hope that.

It helps to answer your questions around those points and then I'll turn it over to Amanda with regards to <unk>.

To answer the question regarding the multimedia disease agitation trial.

Great. Thanks, Yeah, So a great point about being agitation trials as a reminder, this is a randomized withdrawal study. So it's a two purion study where patients were enrolled and randomized and then the trial completion is actually a really contingent upon the number of relapses, which occur so based upon.

Amanda: Thanks for the questions. I'll turn the agitation question over to Amanda, who will provide some color on the trial and maybe some of the unique aspects of the trial and how that would impact interpreting enrollment trends there. But I'll start by first answering your other questions.

All of those variables.

We've been tracking this study we are anticipating the study to complete in the first half. So it's just a slightly complex study design, which which.

Ariel: In terms of the timing of when we got the communication from the FDA on these deficiencies, we recently got them, so very end of October. And since then, we've been trying to get details on them so that we can specifically respond. So we're still in the process of getting those details. And in terms of what you characterize as the unusual nature of this process, it is a unique situation. But remember, it is actually not unusual to receive information requests from the FDA during an NDA review where they might ask for additional information, whether that be in any discipline and including CMC, as we have received.

But again, it's all these different metrics that we're tracking related to enrollment.

Okay.

Okay. Thank you.

Your next question comes from Ram <unk> of H C Wainwright.

Thank you very much for taking my questions.

Just kind of following on from what others have already asked I just wanted to clarify whether at this point you have clarity on if the FDA is going to issue a C. R. L. At some point on a S. S O five or if you think the currently outstanding matters can be resolved without the C. R.

Ariel: So we don't view this information request from the FDA as unusual in and of itself. So I hope that that helps to answer your questions around those points, and then I'll turn it over to Amanda with regard to who will answer the question regarding Alzheimer's disease education. Great, thanks. Yeah, so great point about the

Well in fact, having to be issued and if a C. R. L is going to be a food and I'm not saying that that's going to be the case I don't know if a C. R. L is going to be issued then ultimately given what you currently know about the deficiencies that remain outstanding.

What would you expect a resubmission of the NDA for access so five to be classified as class one or class two.

Amanda: The agitation trials; as a reminder, this is a randomized withdrawal study.

Okay.

Thank you Ron for the question so.

Amanda: So it's a two-period study where patients are...

The first thing is is our is.

Whether or not to your question around whether or not a CR L. He's going to be issued in that is.

Amanda: Rolling, Randomized, and then the trial completion is actually really contingent upon the number of relapses.

That would be an action and FTE action so.

And we don't determine that you have to eat determines that now.

Now what we can tell you is that.

Amanda: [inaudible] Okay, thank you. Your next question comes from Ram Selvaraju of H.C. Wainwright. Thanks so much for taking my questions.

As we stated in our press release and in the opening comments.

D. A has stated that these deficiencies.

With regards to analytical methods.

It must be addressed before they can take action and and action and action on the on the NDA would come in two forms it could be either one.

Raghuram Selvaraju: So, kind of following on from what others have already asked, I just wanted to clarify whether at this point you have clarity on if the FDA is going to issue a CRL at some point on AXS05 or if you think the currently outstanding matters can be resolved without a CRL, in fact, having to be issued. And if a CRL is going to be issued, and I'm not saying that that's going to be the case, I don't know.

And approval war, a CRM and so and.

What the FDA has asked us to do is to provide them information to resolve the deficiencies that must be done prior to them, taking one of those actions I hope it is.

Helpful.

So just as a clarification to what you just said area that means that it still remains possible that.

Raghuram Selvaraju: But if a CRL is going to be issued, then you know, ultimately, given what you currently know about the deficiencies that remain outstanding, what would you expect resubmission of the NDA for AXS05 to be classified as class one or class two? Thanks.

When you submit this information to the FDA the agency will decide not to issue a CLO.

So possible right I don't want you to kind of a handicap for us what the odds of that happening, but just clarify for us whether that is it possible that the FDA.

Ariel: Thank you, Ram, for the question. The first thing is whether or not your question concerns whether or not a CRL is going to be issued, and that is an action, an FTE action, so. And we don't determine that. The FDA determines that. Now, what we can tell you is that, as we've stated in our press release and in the opening comments, the FDA has stated that these deficiencies, with regard to analytical methods, must be addressed before they can take action.

With me not.

Ultimately this U S E R. L on aircraft so five once they see the data and submit.

Yeah.

The reason why I'm hesitating in answering your question is is the way you've posted which is a negative as it is.

And the presumption is that there would be a P. R L and they would not issue with Euro I guess, what we're saying is a is that a is the the agency clearly has not taken action on the NDA and so.

Ariel: And an action on the NDA would come in two forms, an approval or a CRL. What the FDA has asked us to do is to provide them with information to resolve the deficiencies. That must be done prior to them taking one of those actions.

So that's which means that if they have not issued a C. O L. They also have not approve the product.

Those are the two potential outcomes and before they make their decisions they've indicated very clearly to us that they would like the information that they requested.

We're working to make sure that we understand exactly what it needs to go into that response, and and we will do that expeditiously.

Ariel: I hope that that is clear. So just as clarification to what you just said, Ariel, that means that it still remains possible that when you submit this information to the FDA, the agency will decide not to issue a CRL. That's still possible, right?

Okay, and then just on the CMC information that is being requested.

I'm assuming based on.

The responses you gave to some earlier questions that in fact, this EMC information pertains to character further characterization of the product as opposed to any change in the actual product itself. So this would not affect not only you know ongoing clinical studies, but would not.

Ariel: I don't want you to, you know, kind of handicap for us what the odds of that happening are, but just clarify for us whether that is indeed still possible, that the FDA may not ultimately issue a CRL on AXS05 once they see the data that you submit. The reason why I'm hesitating in answering your question is the way you've posted, which is in the negative, as if the presumption is that there would be a CRL and they would not issue a CRL.

<unk> require any further bridging work down the line.

In order to ensure not only that the product is approvable in MTBE, but another indications for which you ultimately may seek approval is that correct.

Ariel: I guess what we're saying is that the agency clearly has not taken action on the NDA, so that means that if they have not issued a CRL, they also have not approved the product. Those are the two potential outcomes. Before they make their decision, they've indicated very clearly to us that they would like the information that they've requested. We are working to make sure that we understand exactly what needs to go into that response. And we will do that expedition.

That is correct.

Okay, and then just very quickly on the smoking cessation.

Clinical program.

Have you received information yet from the FDA regarding specific design parameters of this program, including in particular the.

The extent to which the agency wants to see long term follow up long term evidence or impact on smoking cessation or does that still remain to be determined at this point.

Ariel: Okay, then just on the CMC information that is being requested, I'm assuming based on, [inaudible] That is correct. Okay, and then just very quickly on the smoking cessation clinical program. Have you received any information yet from the FDA regarding specific design parameters of this program, including, in particular, the extent to which the agency wants to see long-term follow-up long-term evidence of impact on smoking cessation? Or does that still remain to be determined at this point?

So what.

The point of on the <unk>.

<unk> meeting guidance.

To get the agencies.

Input on our own an entire clinical development plan to get our excess of five approved for smoking cessation. So that would include.

The design of the pivotal trials of subsequent trials and also a safety database. So.

Ariel: So the point of the pre-IIT meeting guidance was to get the agency... input on an entire clinical development plan to get XSO5 approved for smoking cessation. So that would include the design of the pivotal trials, of subsequent trials, and also of the safety database. Coming out of that process, we do have very clear guidance, which is why we've stated that based on that information, we can proceed to a pivotal trial.

Coming out of that process, we do have a very clear guidance.

Which.

Which is why we.

We stated that our base based on that information. We can proceed into a pivotal trial and so we.

We can do that we're very excited about that and I think.

We are able to leverage and we have been able to leverage all of the data that has been generated with excess of five in in other indications and in both the long term as well as the short term setting.

Ariel: And so we can do that. We're very excited about that. And I think, You know, we are able to leverage, and we have been able to leverage all of the data that has been generated with AXS05 in other indications, in both the long-term as well as the short-term setting. So the answer is yes.

So so.

So you know.

The answer is yes, I think we do have a lot of information on the long term safety of eggs and so five and we believe that we'll be able to leverage that information for the development of excess ore body and smoking cessation.

And just to clarify with respect to the smoking cessation program.

Ariel: I think we do have a lot of information on the long-term safety of XSO5. And we believe that we'll be able to leverage that information for the development of XSO5. And just to clarify, with respect to the smoking cessation program, the FDA has already agreed that if this Phase 2, 3 study results in a positive outcome, you would be able to file on the basis of that for approval in smoking cessation. And do you have a sense of whether the smoking cessation Phase 2, 3 study could yield data before the end of 2022? Or is it more likely to be a 2023 event?

Yeah has already agreed that if this phase two three study results and a positive outcome that you would be able to file on the basis of that foreign approval in smoking cessation and do you have a sense of whether the smoking cessation phase II III study could yield data before the end of 2022 or is it more likely to be a 2023.

Thank you.

We.

The guidance that we've given is that we will provide.

Further guidance on the exact timing of the initiation of the phase two three trial next year.

Ariel: So the guidance that we've given is that we will provide further guidance on the exact timing of the initiation of the Phase 2-3 trial next year, and part of that is for planning purposes.

And part of that is just for planning purposes, we have.

A lot going on 20 years, which are currently filed and incredibly rich pipeline.

Ariel: We have a lot going on, two NDAs which are currently filed, an incredibly rich pipeline, and looking at 2023, we could be filing three more NDAs then, potentially, depending on the outcome of a lot of these studies. So there's a lot going on.

And looking at that.

2023, we could be filing three more NDA has been potentially depending on the outcome of a lot of these studies. So there's a lot going on.

We are scaling up in terms of our capabilities.

Too to make sure that we can take advantage of all of these opportunities.

Ariel: We are scaling up in terms of our capabilities to make sure that we can take advantage of all of these opportunities. And so, that's why, you know, we would like to take our time and make sure that we can provide you with very precise guidance around when we would start that trial, guidance that we can have confidence in, and we will do that next year. And with regard to the pivotal nature of these studies, the Phase 2-3 trial would be a pivotal trial, and we believe that, based on the guidance, we would need two studies in this indication. So the Phase 2-3 trial would be one of those two studies. Thank you.

So that's why.

We would like to take our time and make sure that we can provide you.

With 30 precise guidance around when we would start that trial guidance, but we can have confidence in saying, we will do that next year.

And with regards to.

The pivotal nature of these studies.

The phase III trial would be a pivotal trial and we believe that based on the guidance that we would need two studies in the indications. So the phase three trial would be one of those two studies.

Thank you.

Your next question comes from Joon Lee of Truest Securities.

Joon So Lee: Your next question comes from Joon Lee of Truist Securities. You mentioned that deficiencies could be resolved near to midterm. Can you define what that means? Is that weeks, months, or quarters? And then you stated that all the offers have been made for the sales force, but that they're contingent upon approval. Is there an expiration date on those offers?

Thanks for the updates.

You mentioned that the efficiencies could be resolved near to midterm.

Can you define what that means that niques months or quarters, and then you stated that all of the offers have been made for the salesforce, but.

Our contingent upon approval is there an expiration date on those offers thank you.

Lori Englebert: Thank you. I'll let Lori take the second question. So the current contract, as it states, and we're thinking through June, so depending upon additional clarity from the FDA, how we leverage the offers that are already outstanding, the field force that we've been able to, Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES, I'm incredibly impressed. And so we would like to be able to leverage. Keeping them, but we really need additional clarity in terms of timing from the FDA. And then with regard to what year-to-midterm means, it's weeks to months, and that really depends on.

Sure.

Lori take pick the second question sure.

So the current contract as it states and we're thinking through June so depending upon additional clarity from the FDA, how we how we leverage the offers that are already outstanding.

There you know the field force that are that we've been able to to have offers extended to you.

Their caliber is yeah.

Credibly impressive.

And so we would like to be able to leverage them keeping them, but we really need additional clarity in terms of timing from the FDA before we can make that decision.

Right.

And then with regards to our what near to mid term means that it's weeks to months and that really depends on the.

Mark L. Jacobson: We're waiting on the further feedback that we get from the FDA. Great, and then will you make a press release once you have submitted the responses to deficiencies? So you.

Further feedback that we get from the FDA.

And we're waiting on that feedback.

Great and then would you press release once you have submitted those.

Responses to deficiencies.

So.

Mark L. Jacobson: We, um... We want to provide as much information as we can to you, to investors, to stakeholders, given the unique situation that we are in with regard to NDA-4AXS05. But we also want to balance that with the fact that we are still undergoing review. And historically, we have not provided details of the back and forth with the agency during the review because, as you can imagine, this is a fluid situation, and it remains a fluid situation. So we do want to balance disclosures and also expectations. So do not expect that we will be giving a play-by-play.

We.

We want to provide as much information as we can to.

To you to investors to stakeholders given the unique situation that we are in with regards to the NDA for access so five.

But we also want to balance that with the fact that we are still.

Undergoing review and historically, we have not provided details of the back and forth.

With the agency during the review because as you can imagine it is a fluid situation and it remains a fluid situation. So would you want to balance.

Disclosures and also expectations. So do not expect that we will be giving a play by play we don't think that that would benefit the process. The NDA review process.

Mark L. Jacobson: We don't think that that would benefit the process, the NDA review process with the agency. However, we do intend to update the street on any definitive developments. Thank you. Your next question comes from Mark Goodman of SVB Levering. Hi Herriot.

But with with the agency. However, we do attempt to update the street on any definitive developments.

Great. Thank you.

Your next question comes from Marc Goodman.

SBB Leerink.

Hi, how are you I have a couple of questions first of all if you just simplistically think about an NDA with three section CMC safety and efficacy has the FDA signed off.

Mark Goodman: I have a couple of questions. First of all, if you just simplistically think about an NDA with three sections, CMC, safety, and efficacy, has the FDA signed off on the safety and efficacy portions, or do you not even have those signed off on yet? So if you think about it simplistically, I agree that those would be the main sections, but the process, unfortunately, is not necessarily a simple process.

On the safety and the efficacy portions or you don't even have those signed off on yet.

Yeah.

So if you if you think about it simplistically.

I agree that those would be the main sections with the problems with the process. Unfortunately is not necessarily simple process.

The and <unk>.

What the FDA does is.

Ariel: What the FDA does is, as it reviews the NDA, it does ask sponsors for information that it needs for its review. And right now, the information that has been requested is around CMC, and that's what we are responding to. We have not gotten any notice from the FDA on other deficiencies in other disciplines. So we've not gotten... So you've got no...

It reviews, the NDA it does ask sponsors for information, which it needs fourth review, so and right now the information which has been requested.

We've discussed which is around CMC.

And that's what we are responding to them, we have not gotten any notice from the FDA on other deficiencies in other disciplines. So see if you have not gotten too but your feedback from the FDA you don't know whether they need something with respect to efficacy whether you've got two placebo controlled studies.

Mark Goodman: But your feedback from the FDA, you don't know whether they need something with respect to efficacy, whether you've got two placebo-controlled studies that are good enough, like, you don't know that yet, or you do know that, that you're good on that part of it. I think that when sponsors know that the FDA is fully satisfied is once they've approved the product. And before that, they are doing their job, which is to review the NDA.

Good enough like you don't know that yet or you do know that that you're good on that second part of it.

I think that.

When sponsors know that the FDA is fully satisfied as a once they improved the product.

And before that before that.

They are doing their job, which is to review the NDA and and our job is to respond to them.

Mark Goodman: And our job is to respond to that. Oh, I understand. I'm just trying to understand whether there's been a discussion about the studies yet and your, you know, and the safety of that aspect, the other stuff besides the CMC. You've had that, any discussions there yet? Well, the FDA has been reviewing the application, so they have certainly been reviewing the efficacy, as well as the safety, portions of the NDA. And I think your question was whether or not they had signed off, and we don't know of any specific process whereby they sign off on any specific aspects of the application until they have approved it.

Oh I understand I'm, just trying to understand whether there's been a discussion about that.

The studies, yeah, and your and the safety of that aspect the other stuff. Besides the CMC you've had that just any discussions there yet.

While the FDA has been reviewing the application. So they have certainly been reviewing the efficacy is.

Well as a as well as the safety portions of the NDA.

And I think your question was whether or not they had signed off and we don't know of any specific process whereby the sign off.

On any specific aspects of the application until they have approved it.

Ariel: Right, of course. Maybe the better question is, have there been interactions back and forth with SBA on the safety data and the efficacy data? Oh, there has been interaction with the agency. As one would expect given the stage of the, And just to flip to the CMC for a section, I had thought that CMC was okay. I thought we were okay there, and I presume that you did too. So what kind of came out of the woodwork here to surprise us?

Right of course, maybe its better question is have there been interactions back and forth with SBA on the safety data and the efficacy data.

Well there has been interaction with the agency.

Gotcha.

<unk> of the NDA as one would expect given the stage of the review.

And just to flip to the CMC for section I had thought that CMC.

Okay I thought we were okay. There.

And I presume that you did too so what kind of came out of the woodwork here to surprise us.

Mark Goodman: And then secondly, I forgot, I think it might have been in the Q&A, the first question. But the response was, you know, we're working to update the analytical methods. We're still trying to figure out exactly what the FDA needs. So how can you feel comfortable that it's been weeks to months when you're still not exactly comfortable with what the FDA needs? So it takes weeks to months for us to complete the work that we need to complete.

And then secondly.

Forgot I think it might have been in the Q&A on.

The first such first question, but their response was you know we're working to update the analytical methods, we're still trying to figure out exactly what the FDA needs.

So how can you feel comfortable that it's weeks to months when you're still not exactly comfortable with what the FDA needs.

So the so we started weeks to months for us to complete.

The work that we need to complete.

Ariel: And then the reason why it is weeks to months, or actually we said near to intermediate term, that is meant to reflect the fact that we need to get more specifics from the FDA in terms of what will go into the response. And then, with regard to your other question around CMC, the review is ongoing, and as part of the ongoing review, it is typical for sponsors to get information requests along the way.

And then the reason why it is a weeks to months of work actually we said near to intermediate term that is meant to reflect the fact that we.

We need to get more specifics from the FDA in terms of what would go into the response.

And then with regards to.

Your other question around CMC.

The review is ongoing and as part of the ongoing review. It is typical for sponsors to get information requests along the way.

Ariel: And it really depends on the rhythm of the review, it depends on the particular reviewer, and so our job is, we can't predict when those requests will occur or what they are, and our job is to make sure that, as the sponsor, we adequately respond to them. Arian, are you willing to help characterize what these two deficiencies are a little better?

And it really depends on on the rhythm of the review.

It depends on the particular review we're independent.

And our job is we can't predict when those requests will occur.

What they are and our job is to make sure that at the sponsor we adequately respond to them, which is what we're what we're doing at an area you're willing to help characterize what these two deficiencies are a little better it's an analytical method and demonstrating that the manufacturing as you know.

Ariel: It's an analytical method for demonstrating that the manufacturing is, you know, so analytical. Analytical methods relate to testing of the finished drug products, or meaning our tablets. This does not relate to the manufacturing process at all.

As good as it needs to be what what exactly we're talking about here.

So analytical.

So analytical methods related to testing of the finished drug products are meeting our tablets. This does not relate to the manufacturing process.

Ariel: And so you can make analytical methods more sensitive or less sensitive. You can broaden the range or narrow the range. And we have what we believe to be a pretty robust process. And you can make it more robust or less robust, more sensitive or less sensitive.

At all and so you can make analytical methods are more sensitive or less sensitive you can broaden the range.

Or narrow the range and and and we have a what we believe to be a pretty robust process.

And you can make it a more robust or less robust more sensitive or less sensitive.

And we are responding to the Fda's request and we think that those.

Ariel: And we are responding to the FDA's request, and we think that... Those are totally addressable, and those are things that we can address. Thank you. Just one quick question on the migraine.

Those are totally addressable and those are things that we can do.

Thank you just one quick question on the migraine can you just help.

Mark Goodman: Can you just help us understand? Did you say that one of the two manufacturing sites might not be able to be signed off on by the PDUFA date? So you're implying that one could be, and is one enough? Do both have to be?

As I understand did you say one of the two manufacturing sites might not be able to be signed off on by the <unk> date, So you're implying that one could be in its want enough do both have to be thought I was a little confused by your comments. Thank you yeah yeah.

Kevin: I was a little confused by your comment. Thank you. Yeah, so I'll turn it over to Kevin, who will respond to that. But I think it's pretty straightforward in terms of what the FDA is. Trying to keep his head up there.

Yeah, so what.

I'll turn it over to Kevin who will respond to that but I think it's pretty straightforward in terms of what the FDA is trying to give up on there.

Kevin: Thanks. Thanks for that question. So, you know, there are obviously multiple manufacturing sites involved in the process for AXS07. The FDA notified us that one specific manufacturing location that is based in the United States is required to have an inspection prior to it as part of the review process. And then they did notify us that, you know, that because of COVID-related restrictions, that may be in jeopardy of happening before the PDUFA date. So it's just this one manufacturer based in the United States that they specifically notified us of in their communication.

Okay. Thanks for that question. So there are obviously multiple manufacturing sites involved in the process for access was seven.

<unk> notified us that one specific manufacturer manufacturing location that is based in the United States.

Is required to have an inspection prior to them as part of the review process.

They did notify us that.

Because of Covid related restrictions that may be in jeopardy of happening before that date. So it's just this one manufacturer based in the United States that they specifically noted by us.

In their communication.

Vikram Purohit: Your next question comes from Vikram Purohit of Morgan Stanley. Great. Good morning. Thanks for taking our questions. So, two from our side.

Okay.

Thank you.

Your next question comes from Vikram pure ahead of Morgan Stanley.

Great. Good morning, Thanks for taking our questions.

So two from our side first going back to again, Oh five for <unk>. So I just wanted to clarify one basic question around next steps. So here's the situation basically that you've now submitted questions for clarification to the agency and you're waiting to hear back or.

Vikram Purohit: First, going back to 05 for MDD. So I just wanted to clarify one basic question around next steps. So is the situation basically that you've now submitted questions for clarification to the agency, and you're waiting to hear back? Or are you preparing a submission in response to the initial feedback you got, which could take weeks to months, and then after that, submission, you'll get some clarification on some more specifics around what the agency And then secondly, Beyond05, who had a question on AXS14 and fibromyalgia. So your release mentions that an NDA submission is expected in 2023, and I was just wondering if you could walk us through what needs to happen between now and then to enable the filing. Thank you.

Are you preparing.

The submission in response to the initial feedback you've got which could take weeks to months and then after that.

Submission, you'll get some clarification on.

Some more specifics around what the agency might.

It might be looking for and then secondly beyond O. Five set of question on excess 14 in fibromyalgia. So your release mentioned that.

Submissions expected in 2023, and I was just wondering if you could.

Walk us through what needs to happen between now and then to Rob.

To enable a filing thank you.

Sure.

Ariel: So with regard to the first question, that is correct; we have submitted clarification questions to the agency, and the reason for that is we want to make sure that when we respond, the response is adequate, and that it is exactly what they need to respond to, to continue their assessment of the end, with regard to CMC. So we don't want to rush to submit a response or to do an experiment and submit it and have it not be exactly what they're looking for. So you are correct.

So with regards to the first question that is correct and you know we have submitted a clarification questions.

To the agency and the reason for that is we wanted to make sure that.

When we respond that the response is adequate and that it is exactly what they need to.

Two two.

To continue their assessment of the NDA.

With regards to CMC. So so we.

We don't want to.

Rush too.

Submit a response or to do an experiment and submitted and have it not be exactly what they were before so to that so you are correct.

And with regards to excess 14 four.

Ariel: And with regard to AXIS-14 for fibromyalgia, what needs to happen right now is primarily CMC manufacturing. As a reminder, AXIS-14 is a new chemical entity. So we do have to synthesize the material, which we are working to do, and then also generate the stability data. So most of the work, and certainly the rate-determining steps in filing the NDA, has to do with many.

<unk> for fibromyalgia.

What needs to happen right now is primarily a CMC manufacturing as a reminder, excess 14 is a new chemical entity.

<unk>.

So we do have to synthesize.

The material, which are which we are working to do and then also generate stability data. So most of the work.

And certainly the rate determining steps in filing the NDA has to do with that.

With manufacturing.

Vikram Purohit: Okay, I got it. Thank you.

Okay got it thank you.

Ashwani Verma: Your next question comes from Ashwani Verma of Bank of America.

Your next question comes from Ashwin <unk> pharma of Bank of America.

Ashwani Verma: Hi there. Thanks for taking our questions. So I wanted to understand, like, I think there's a lot of discussion about just these deficiencies, which seem pretty complex to me. I mean, can you give us some confidence that your team or any external partners that you have will be able to navigate through this? Has your team or any regulatory consultant that you have hired handled such a specific situation before? That's my first question.

Hi, there.

Thanks for taking our questions.

So I wanted to understand like I think there's a lot of discussion on just these deficiencies. It seemed pretty complex to me I mean can you give us some confidence that our team at any external partners that you have will be able to.

Navigate through this.

Jim or any regulatory consultant that you have as high as it.

It has hundreds of just specific situations before.

That's my first question and the second one just on the analytical methods. So would you need to redo some experiments scared them anything downstream of that are.

Ariel: The second one just on this analytical method. So would you need to redo some experiments here or anything downstream of that or the deficiency in the method specifically? What does that mean in terms of resolving it? Would that need to be done, or just needs to be characterized better the findings that you had from that experiment?

Great.

He did the efficiency and the metrics specifically.

What does that mean in terms of resolving it would that need to be done or that just needs to be characterize better. The findings that you had from that next payment.

Ariel: To answer those questions, this is the reason why we are making sure that we get as much clarification from the FDA as possible, and that's what we're doing. So we want to get clarification from the FDA, and then with regard to the actual deficiencies themselves, and just if you kind of step back, so first of all, we did say that we believe that they are addressable, and we're very confident in that, but if you step back, a lot of these requests or this type of request is not unusual during an NDA review.

So.

Yeah.

Answer those questions as is the reason why we are making sure that we get as much clarification from the FDA as possible.

And and so.

And that's what we're doing so we want to get clarity from the FDA and then with regards to the.

The actual deficiencies themselves.

And.

If you kind of step back so first of all we did say that we believe that they are addressable so and we're very confident.

In that.

But if you step back.

A lot of.

A lot of these are these requests where this type of request is this is not unusual during an NDA review.

Ariel: The only reason why we're discussing it right now is because, you know, we're past BDUFA and given the unique situation, so we want to provide you guys with as much information as possible that is relevant to this unique situation. But, you know, the nature of the requests themselves are probably not... Unusual though these are the types of requests which, normally, we think would come up during the review of other sponsors' NDAs during a normal NDA review cycle.

Only reason why we're discussing it right now is is because you know where we're past Purdue and given the unique situations.

We want to provide you guys.

As much information as possible that is relevant to this unique situation.

But the nature of the request themselves are probably not.

Unusual.

These are the types of requests which.

Normally.

We think would come up.

During our review of other sponsors NDA stirring and normal India review cycle.

Ashwani Verma: Just a quick follow-up, if I had like, so the field force bill is complete, you said, how many reps are we talking about? I mean, this is a big market, a lot of different types of prescribers. What's your approach going to be? Are you focused on prior dexamethorphine prescribers or branded prescribers or any other ways to penetrate the market?

Okay.

Just a quick follow up if I had like so the feet of steel post spin. This compete it said how many of that that'd be talking I mean, and this is a big market a lot of defense.

Types of prescribers, what's your approach going to be are you focus on prior decks of metallics and prescriber I saw a branded prescribers all of any of the.

Based on the market.

Lori Englebert: Yeah, thanks, Ash. So, you know, I'll speak more to the size of the Salesforce when we when we get prepared to launch. I don't want to disclose that right now, but I will tell you that we will personally promote to what we believe will be 85% of the high-value prescribers in the market. And that's a very complex algorithm for determining what high-value prescribers are, but they will cover, you know, greater than 25,000 HCPs from a personal point of view. From a non-personal promotion basis, we will also... [inaudible] Thank you. Your next question comes from Matt Kaplan, Wadenburg, Salomon. Hi, thanks for taking the question. I guess it is.

Yes, I think thats.

So I'll speak more to the size of the sales force when when we when we.

Get prepared to launch a I don't want to disclose that right now, but I will tell you that we will personally promote to what we believe will be 85% of the high value prescribers in the marketplace.

And that's a very complex algorithm of determining what high volume prescribers are.

But they will cover greater.

Greater than 25000, Acp's on a personal promotion basis.

From a non personal promotion basis, we will also you.

Hmm.

B targeting additional acp's.

Thank you.

Your next question comes from Matt Kaplan Ladenburg Thalmann.

Hi, Thanks for taking my question.

I guess.

Matthew Lee Kaplan: Going into the deficiencies a little bit more on this unusual process, you mentioned that the action of the FDA could be either to approve the product or potentially issue a CRL. I guess beyond that, given the unusual situation, could your answers to the CMC questions be deemed a major amendment, and would they issue you a new PDUFA date, or are you just going to be running through this process with the FDA without a new specific action date? Thanks Matt for the question. So when the FDA misses a PDUFA date, there is no new PDUFA date that is issued.

Going into the deficiencies a little bit more on this unusual process, you mentioned that kind of the action of the FDA could be either to approve the product or.

Our potentially issue with C. R. L I guess.

Beyond that given the unusual situations could your answers.

The answers to the CMC questions be deemed a major amendment.

And would they issue you are a new but do you have a date or theirs. We're just you're just going to be running through this process with the FDA without a specific.

A specific action date.

Thanks, Matt for the question.

So when when.

When the FDA.

Mrs.

<unk> date, there is no <unk> date, which is a which is issued.

Okay. Okay. That's helpful.

Matthew Lee Kaplan: And I guess a question with respect to commercial preparation, given the unique profile of O5, what's your sense or what's your feedback from potential payers at this point in terms of potential coverage and thinking about pricing? Yeah, thanks, Matt. So, you know, I previously mentioned that we've had our National Account Directors in the field having permitted payer discussions since about April, and you know all discussions have been highly encouraging. But we will not engage in discussions, you know, formal discussions with payers until after approval and once we have a final label.

And I guess huh.

Question with.

With respect to our commercial preparations.

Given the unique profile of Ohio.

What's the what's your center, what's your feedback from potential players at this point in terms of.

Actual coverage and and thinking about pricing.

Yeah, Thanks, Matt so.

Previously mentioned, we've had our national account directors in the field, having permitted payer discussions since about the April timeframe.

And you know all discussions have been highly encouraging.

But we will not engage in discussions formal discussions with payers until after approval and once we have a final label.

In terms of pricing will be prepared to reveal that at launch, but you know our goal is to make sure that patients receive access but that we capture the value that that product brings to market.

Matthew Lee Kaplan: In terms of pricing, we'll be prepared to reveal that at launch, but our goal is to make sure that patients receive access but that we capture the value that the product brings. Thanks for taking the questions. Your next question comes from Yatin Suneja of Guggenheim. Hey guys, thank you.

Yeah.

Thanks for taking the questions.

Your next question comes from data Sydney.

<unk> of Guggenheim.

Hey, guys. Thank you.

Yatin Suneja: Just maybe a couple questions for me. Could you enter into labeling discussions prior to addressing these deficiencies, or if the FDA is okay with the clinical section, could you enter, or once you submit to CMC, once they're satisfied, only then can you enter? So that's the first question. And I understand these CMC deficiencies, you know, more are analytical, more related to the analytical method, but are we sure that there is no physical visit or any inspection, anything required by the FDA at this point?

Just maybe a couple of questions from me.

Could you enter into labeling discussions prior to addressing the deficiencies or.

When the if the FDA is okay with the clinical section could you enter or once you submit to CMC on say a Chinese only then you can and so that's first question and I understand the CMC deficiencies.

Murat anything that's more related to I know that doesn't matter, but I assure that there is no physical visit or any inspection anything required by the FDA at this point.

Yatin Suneja: Thanks for the questions, Yatin. The deficiencies with regard to CMC have not been characterized to us by the agency as ones that would preclude labeling discussion. You know, just to be clear, you know, we will not be commenting on when we enter into labeling discussions, but... You can't answer your question, you know, these are not... Deficiencies which were characterized as ones that would preclude labeling discussions. And in terms of inspections, we have not been made aware that there are inspections which need to be done prior to the approval of AXS 05.

Okay. Thanks.

Thanks for your questions.

Yeah.

The.

The deficiencies with regards to CMC.

They have not been characterize to us by the agency as ones that would preclude labeling discussions.

No just to be clear, we will not be commenting on when we enter into labeling discussions about.

To answer your question these are not.

<unk>, which were characterized as is once that would preclude.

Labeling discussions and in terms of inspections.

We have not been made aware that they have or inspections, which need to be done.

Prior to the approval of <unk> five.

Ariel: And I don't know if... You know, if Kevin has any information in terms of the pace or rhythm of inspections, the regular rhythm of inspections at the... Manufacturers that we use for ecosystems. Cut it, yeah.

And I don't know if.

Yeah.

Kevin has any information in terms of.

The pace will rhythm of of inspections, the regular rhythm of inspections at the.

Manufacturers that are that we use weka survive.

Got it.

Yatin Suneja: I think, Kevin, I have a question. Obviously, you are making progress in terms of the commercial launch. Can you give some color in terms of the pair discussions? How should we think about price?

I think Kevin I did do I have a question on the one more question.

I mean, obviously you were making.

In terms of the commercial launch can you give some color.

So of the payer discussions.

How should we think about price any consideration in terms of you know maybe good comp for us to see them in the in the field in terms of how we should be monitoring the price. The ones. You know once you get approved and launched.

Yatin Suneja: Any consideration in terms of maybe good comp for us to see in the field in terms of how we should be modeling the price? You know, once you get approved, and it's, Yeah, thanks, Yatin. So, you know, consistent with what was just mentioned, we have had some very encouraging payor discussions to date, but those have been in a permitted fashion where we specifically introduced Axsome, and the clinical profile of AXS05. We will not engage in discussions.

Yeah, Thanks, Jonathan so consistent with what.

As I've mentioned, we have had some very encouraging payer discussions to date.

But those have been in a in a permitted fashion when we specifically introduced axiom the clinical profile of in excess of five we will not engage in discussions.

Lori Englebert: We won't have any formal discussions with them until after approval and once we have the final design. In terms of price, I think payers do recognize an unmet need in the marketplace. They also recognize that AXS05 does have a novel mechanism of action and the clinical benefits that the product can bring to market. So in terms of price, as I mentioned earlier, the way that we'll approach it, and we will be in a position to, you know, announce price at approval, is that our goal really is to make sure that patients have easy access to the product, but that we as a company capture the value that the product brings. We do have time for two more questioners.

Formal discussions with them until after approval and once we have the final label.

A price.

I think you know payers do recognize an unmet need in the marketplace. They also recognize in excess of five does have a novel mechanism of action and that the clinical benefits that the product can bring to market it could be great.

So in terms of price as I mentioned earlier, the way that we'll approach it in and we will be in a position to announce price it.

At approval.

Is that you know our goal really is to make sure that patients have easy access to the product.

But that we as a company capture the value that's probably right.

Got it thank you.

We do have time for two more questioners. Your next question comes from Myles Minter of William Blair.

Myles Robert Minter: Your next question comes from Myles Minter of William Blair. Hey everyone, thanks for the questions. I may have missed it, but did you just say that the deficiencies that we're discussing today did not preclude labeling discussions? That is correct, so that is right. Right, so it begs the question whether the letter that you received that stated deficiencies that did preclude labeling discussions either still exists, or you're currently in the labeling discussions. Sorry for the difficult question, but I'd love clarification on that. Yeah, so no, thank you for the question. And we do, we do appreciate you trying to parse through.

Hi, everyone. Thanks for the questions.

I might have missed it but did you just say that the deficiencies that we are discussing today.

Not preclude labeling discussions.

Yeah.

That is correct or wash through.

That's right.

Right. So it begs the question that the letter that you received that stated deficiencies that did pre Covid library and discussions.

They still exist.

Or youll currently in labeling discussions.

Sorry for the difficult question, but I'd love clarification around that.

So what no. Thank you for the question and we do we do appreciate.

You're trying to parse through.

Ariel: The situation and what we've done, and what we're trying to do is provide you with the information that we get as soon as possible after we get it. So that's the information that we have received. And we did disclose in the prior letter, and we've also disclosed now the fact that we have gotten some information on deficiencies. And so we don't know if...

The situation and what we've done and what we're trying to do is to provide you.

The information that we get as soon as.

As soon as possible after we get it and so that's the information that we have received so.

Disclose the private letter.

And we've also disclosed.

Now the fact that we have gotten some information on.

Deficiencies that so.

We don't know with it.

Ariel: These deficiencies are the ones that were previously referred to, or if those deficiencies are now a thing of the past, but this is the information that we have. We're actually encouraged that we have gotten this information because that's all we've ever wanted as a sponsor is the ability to address whatever questions that there are that will help the FDA in their NDA review process. Okay, cool. The final one for me is just the NDA filing for 07.

These deficiencies are the ones, which were previously referred to or if those deficiencies or now a thing of the past but.

This is the information that we have and so you know where.

We're actually encouraged that we have gotten this information because that's all we've ever wanted as a sponsor is the ability to address.

Address whatever questions that they are that.

That will help the FDA and their NDA review process.

Okay cool.

Final one from me is just the NDA filing because zero seven does that carry the same analytical measures on the manufacturing level as zero at five in the current filing.

Ariel: Does that carry the same analytical measures on the manufacturing level as 05 in the current filing? Because the products are distinct molecules with different active components, they would not necessarily carry over into the O7 application specifically.

Kevin.

Hi.

Because the products are distinct.

Molecules with different active components, they would not carryover necessarily into the O seven applications specifically.

Myles Robert Minter: Alright, cool, thanks guys. Your next question comes from Joon Lee of Truist Securities. Well, thanks for taking our follow-up. I just wanted to clarify some questions that I've been getting from investors, which is that the analytical method relates to further characterization of the product but not the product itself. I think that's what you said. Can you clarify what you meant by not the product itself? How can you be confident that this is not related to the product itself, or whatever that means?

Alright, thanks, guys.

Your next question comes from Joon Lee of Truth Securities.

Yes.

Well, thanks for taking a follow up.

I wanted to clarify some questions that I've been getting from investors, which is that the analytical method relates to further characterization of the product, but not the product itself. I think that's what you said can you clarify what you mean by not the product itself. How you can be confident that this is not related to the product itself.

That means and the second question is.

Myles Robert Minter: And the second question is, you got the letter from the FDA, or the FDA let you know about the deficiencies in August, but the nature of the deficiencies was not disclosed until late October, is that correct? Or did that happen earlier? Thank you. So the comment around the analytical methods, so we were making a distinction between the manufacturing process and the analytical methods which test the finished goods. And so the analytical process, that's what it tests. The analytical methods, that's what they test, the finished goods. And so. So that was the distinction.

Got the letter from the FDA or.

Let you know about the deficiencies in August but the nature of the deficiencies were not disclosed until late October is that correct or did that happened earlier. Thank you.

So the comment around the analytical methods. So we were making a distinction between the manufacturing process.

And the analytical methods to which test the finished goods and so the analytical process that's what it tests.

The inaugural methods, that's what they test the finished goods and so.

So that that that was the distinction so these.

Joon So Lee: The deficiencies do not relate to the manufacturing process itself, in other words, how the tablets are made. And then, with regard to the timing that you've laid out, that is correct. Thank you. I will now turn the conference back over to the CEO. Well, thank you again, everyone, for joining us on the call today. With four pipeline candidates being developed in six indications, which are either under FDA review or in late stage development, we believe that we have built the leading CNS-focused pipeline in the industry.

The deficiencies that do not relate to the manufacturing process itself.

Now the tablets are made.

And then and then with regards to the timing that you've laid out that that is correct.

Thank you.

Okay. Thank you I will now turn the conference back over to the CEO.

Well. Thank you again, everyone for joining us on the call today.

With four pipeline candidates being developed in six indications, which are either under FDA review.

Or in late stage development, we believe that we have built the leading CNS focused pipeline in the industry.

Joon So Lee: We're working hard to bring these potentially life-changing medicines to people who live with serious CNS conditions. We look forward to keeping you updated on our continued progress. Have a great day. Thank you for participating in today's conference call. You may now disconnect.

We're working hard to bring these potentially life changing medicines to people, who live with serious CNS conditions, and we look forward to keeping you updated on our continued progress have a great day.

Thank you for participating in today's conference call you may now disconnect.

Okay.

Okay.