Q4 2020 Axsome Therapeutics Inc Earnings Call

Ladies and gentlemen. This is your operator today's call is scheduled to begin momentarily until that time. Your line will again be placed on music hold thank you for your patience.

Operator: and this is your operator. Today's call is scheduled to begin momentarily. Until that time, your line will again be placed on music hold. Thank you for your patience. ??? ??? ??? Good morning and welcome to the Axsome Therapeutics conference call. Currently, all participants are in a listen-only mode. Later, there will be a question and answer session, and instructions will follow at that time. As a reminder.

Operator: Today's conference call is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, Chief Operating Officer at Axsom Therapeutics. Please go ahead.

[music].

Mark L. Jacobson: Thank you, operator. Good morning, and thank you all for joining us on today's conference call. Our earnings press release providing a corporate update and details of the company's financial results for the fourth quarter and full year of 2020 crossed the wire a short time ago and is available on our website at Axsome.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our investigational agents; our clinical and non-clinical plans; our plans to present or report additional data, the anticipated conduct and source of future clinical trials, regulatory plans, future research and development plans, commercial plans, and possible intended use of cash and investment.

Good morning, and welcome to the Axiom Therapeutics Conference call.

Currently all participants are in a listen only mode. Later, there will be a question and answer session and instructions will follow at that time as a reminder.

Today's conference call is being recorded I would now like to turn the conference over to your host Mark Jacobson, Chief operating officer at acts and Therapeutics. Please go ahead.

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

Our earnings press release, providing a corporate update and details of the company's financial results for the fourth quarter and full year of 2020 crossed the wire a short time ago and is available on our website at <unk> Dot com.

Mark L. Jacobson: 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 forward-looking statements, which are made only as of today's date, and the company disclaims any obligation to update such 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.

Our plans to present or report additional data the anticipated conduct and the source of future clinical trials regulatory plans and 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 forward looking statements.

Mark L. Jacobson: Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Lori Englebert, Senior Vice President of Commercial and Business Development; Dr. Amanda Jones, Senior Vice President of Clinical Development; and Dr. Cedric O'Gorman, Senior Vice President of Medical Affairs. Ariel will first provide an overview of the company and then review recent developments and upcoming milestones. Following Ariel, Nick will review our financial results, and we will then open the line for questions. And with that, I will turn the call over to Ariel.

For these and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our record early and annual reports you are cautioned not to place undue reliance on these forward looking statements, which are made only as of today's date and the company disclaims any obligation to update such statements.

Joining me on the call today are Dr area to Buteau, Chief Executive Officer, Nick Peasy, Chief Financial Officer, Lori Inglebert Senior Vice President of commercial and business development, Dr. Amanda Jones Senior Vice President of clinical development and Dr. Cedric O'gorman Senior Vice President of Medical Affairs.

<unk> will first provide an overview of the company and then review recent developments and upcoming milestones.

Following Ariel Nick will review our financial results. We will then open the line for questions and with.

Ariel: Thank you, Mark. Good morning, everyone, and thank you all for joining Axsome Therapeutics' fourth quarter and full year 2020 financial results and business update conference call. This past year was one of focused execution for Axsome as we advance our industry-leading CNS pipeline towards marketing application submission. Our portfolio comprises four late-stage product candidates under development for six distinct indications representing unmet medical needs that affect over 60 million patients in the U.S. alone.

That I will turn the call over day area.

Thank you Mark good morning, everyone and thank you all for joining exome therapeutics fourth quarter and full year 2020 financial results and business update conference call.

This past year was one of focused execution for <unk> zone, as we advance our industry, leading CNS pipeline towards marketing application submissions.

Our portfolio comprises for late stage product candidates under development for six distinct indications, representing unmet medical needs that effect over 60 million patients and the U S alone.

Ariel: Our focus this year will be on the regulatory activities surrounding our NDA filings for AXS05 and AXS07, launch readiness to ensure a successful transition to commercialization, assuming product approvals, and continued advancement of the rest of our Elite Stage CNS pipeline. I will provide a brief update on our pipeline and pre-commercial activities before turning it over to Nick, who will provide a financial update.

Our focus this year will be on the regulatory activities surrounding our NDA filings for excess so five and except for seven.

Launch readiness to ensure a successful transition to commercialization and assuming product approvals and.

And continued advancement of the rest of our late stage CNS pipeline.

I will provide a brief update on our pipeline and pre commercial activities.

Before turning it over to Nick who will provide a financial update.

Ariel: Starting with our first lead product candidate, AXS05; the new drug application or NDA for XSO5 for the treatment of MDD has been submitted. We intend to issue a press release following the FTE's decision regarding its acceptance of the filing.

Starting with our first lead product candidate <unk> five.

The new drug application and Wendy Yang for access so five for the treatment of M. D. D has been submitted.

We intend to issue a press release following the Fda's decision regarding its acceptance of the filing.

Ariel: This NDA submission is a major milestone for the company as it brings us closer to potentially making this innovative treatment available to the millions of patients who are living with depression. AXSO5 is a novel, oral, and MDA receptor antagonist with multimodal activity. If approved, AXSO5 has the potential to be the first new oral mechanism of action for depression in over 60 years. In the fourth quarter, we announced positive results from the long-term open-label Phase 3 Comet trial, demonstrating rapid, substantial, and durable improvements in depressive symptoms and functional impairment that were sustained over the 12-month treatment period with AXS 05.

This NDA submission is a major milestone for the company because it brings us closer to potentially making this innovative treatment available to the millions of patients living with depression.

The successful five is a novel oral NMDA receptor antagonist with multimodal activity.

And if approved the excess to five has the potential to be the first new oral mechanism of action for depression and over 60 years.

And the fourth quarter.

We announced positive results for the long term open label Phase III <unk> trial, demonstrating rapid substantial and durable improvements in depressive symptoms and functional impairment that was sustained over the 12 month treatment period with an excess of five.

Ariel: AXSO5 was well-tolerated during long-term treatment, with a safety profile consistent with that observed in the previously-reported controlled trials. We also announced positive results from the Phase 2 Open Label COMET sub-studies in patients failing one prior treatment, failing two prior treatments, and in patients with suicidal ideation. Moving on to our Alzheimer's disease agitation program with AXSO5. Alzheimer's disease agitation is a serious and debilitating condition for which there is currently no approved treatment.

Except for a five was well tolerated with long term treatment with a safety profile consistent with that observed and the previously reported controlled trials.

We also announced positive results from our phase two open label comments sub studies and patients failing one prior treatment failing two prior treatments and in patients with suicidal ideation.

Moving on to our Alzheimers disease agitation program with access or five.

Holzheimer disease agitation is a serious and debilitating condition for which there is currently no approved treatment.

Ariel: Last year, we announced positive results from the pivotal ADVANCE-1 trial, which demonstrated rapid and substantial improvement of agitation in patients with Alzheimer's disease with the XSO5 treatment. We subsequently received breakthrough therapy designation for AXSO5 in this indication. In December, we launched our second pivotal trial, the ACCORD study, which is a double-blind, placebo-controlled, randomized withdrawal study.

Last year, we announced positive results from our pivotal advance one trial, which demonstrated rapid and substantial improvement of agitation in patients with full timers disease with except for five treatment.

We subsequently received breakthrough therapy designation for X and so five and this indication.

In December we launched our second pivotal trial. The court study, which is a double blind placebo controlled randomized withdrawal study.

Ariel: Turning now to our Migraine Program with AXS 07. We are completing the NDA, which we expect to submit to the FDA early in the second quarter. There is a significant unmet need for more efficacious treatment for migraines. The World Health Organization ranks the disability from severe migraine attacks on par with that from dementia, quadriplegia, or active psychosis.

Turning now to our migraine program with except for seven.

We are completing compilation of the NDA, which we expect to submit to the FDA early in the second quarter.

There is a significant unmet need for more efficacious treatment for migraine.

The World Health organization ranks the disability from severe migraine attacks on par with that from dementia quadriplegia for active psychosis.

Ariel: AXS 07's novel, oral, multi-mechanistic approach may help to address this unmet need. In the fourth quarter, we announced positive results from a long-term, open-label, movement trial of XSO7, demonstrating rapid, substantial, and durable relief of migraine pain and associated symptoms over the 12-month treatment period. AXS07 was well tolerated over long-term treatment with a safety profile consistent with that observed in the previously reported control trial. Moving next to our AXS 12 Product Candidate for Narcolepsy. Darcolepsy is a serious and debilitating condition with limited treatment options.

Except for the seventh novel oral multi mechanistic approach may help to address this unmet need.

And the fourth quarter, we announced positive results from a long term open label moving trial of excess and seven demonstrating rapid substantial and durable relief of migraine pain and associated symptoms.

For the 12 month treatment period.

The successful seven was well tolerated over long term treatment with a safety profile consistent with that observed and the previously reported controlled trials.

Moving next to our excess 12 product candidate for narcolepsy.

Narcolepsy is a serious and debilitating condition with limited treatment options.

Ariel: Results from our Phase 2 trial demonstrated the potential for AXS12 to address a broad range of narcolepsy symptoms. We expect to initiate a Phase III trial of XS12 in narcolepsy in the second quarter. For our XS14 product candidate for the treatment of fibromyalgia, we're scheduled to meet with the FDA in the second quarter of this year to discuss the development plan for this program. AXS14 has previously met the primary endpoints in a phase 3 and a phase 2 trial for the treatment of fibromyalgia.

<unk> from our phase two trial demonstrated the potential for excess 12 to address a broad range of narcolepsy symptoms.

We expect to initiate a phase III trial of excess 12, and narcolepsy and the second quarter.

Wow excess 14 product candidate for the treatment of fibromyalgia.

And we're scheduled to meet with the FDA and the second quarter of this year to discuss the development plan for this program.

Except for team has previously met the primary endpoint and a phase III and and a phase two trial for the treatment of fibromyalgia.

Ariel: Our intellectual property portfolio continues to grow with recently issued and allowed patents for XS05 and XS07. The number of issued U.S. patents for these product candidates now total 50 for each, with protection extending to 2040 and 2036, respectively. With potential FDA decisions on two NDE filings over the coming year, preparations for potential commercial launch are well underway. All functional commercial leadership is in place, and the team continues to expand. Sales force structure and design have been finalized, and the hiring of sales managers and representatives will begin shortly.

Our intellectual property portfolio continues to grow with recently issued and allowed patents for a successful five and excess of seven and.

The number of issued U S patents for these product candidates now total 50 for each with protection extending to 2040 and 2036, respectively.

With potential FDA decisions for two NDA filings over the coming year preparations for potential commercial launch and are well underway.

All functional commercial leadership is in place and the team continues to expand.

Sales force structure and design have been finalized and the hiring of sales managers and representatives will begin shortly.

Ariel: The infrastructure for our proprietary DCC, or Digital Central Commercialization Platform, is in place, and Peer Engagement Activities have started. We are excited by the differentiated clinical profile of our numerous product candidates, the potential of our investigational medicines to deliver significant benefits to patients, and our planned commercialization approach. I will now turn the call over to Nick, who will provide a financial update.

The infrastructure for.

And our proprietary DCC for digital centric commercialization platform is in place and <unk>.

Payer engagement activities have started.

We are excited by the differentiated clinical profile about numerous product candidates the.

And the potential that our investigational medicines to deliver significant benefit to patients and our planned commercialization approach.

I will now turn the call over to Nick who will provide a financial update.

Nick Pizzie: Thank you, Ariel, and good morning, everyone. Today, I will discuss our fourth quarter 2020 results and provide some financial guidance. We ended the fourth quarter with approximately $184 million in cash, compared to roughly $202 million at the end of the third quarter, a net decrease of approximately $18 million. R&D expenses were $17.4 million for the fourth quarter ended December 31, 2020, versus $19.2 million for the comparable period in 2019. The decrease of $1.8 million was driven by the completion of a majority of our clinical trials, which were ongoing in the comparable prior period, offset by costs related to the preparation of AXS05 and AXS07 NDAs.

Thank you Ariel and good morning, everyone.

And I will discuss our fourth quarter 2020 results and provide some financial guidance.

We ended the fourth quarter with approximately $184 million and cash compared to roughly $202 million at the end of the third quarter and.

And net decrease of approximately $18 million.

R&D expenses were $17 4 million for the fourth quarter ended December 31, 2020 versus $19 $2 million for the comparable period in 2019.

The decrease of $1 $8 million was driven by the completion of a majority of our clinical trials, which are ongoing and the comparable prior period offset by costs related to the preparation of access so far and excess of seven and NDA submission.

Nick Pizzie: G&A expenses were $10.4 million for the quarter ended December 31, 2020, and $5.2 million for the comparable period in 2019. The change was primarily due to an increase in non-cash stock compensation, along with the continued build out of the commercial function. The net loss was $29.2 million, or $0.78 loss per share, for the quarter ended December 31, 2020, compared to a net loss of $24.8 million, or $0.71 loss per share, for the comparable period in 2019.

G&A expenses were $10 $4 million for the quarter ended December 31, 2020, and $5 2 million for the comparable period in 2019 the.

And the change was primarily due to an increase in non cash related stock compensation expense along with the continued build out of the commercial function.

Net loss was $29 $2 million for 78 loss per share for the quarter ended December 31, 2020, compared to a net loss of $24 $8 million for 71 cents loss per share for the comparable period in 2019.

Nick Pizzie: The net loss for the year ended December 31, 2020 was $102.9 million, or a loss per share of $2.77, compared to a net loss of $68.3 million, or a loss per share of $2.01, for the comparable period in 2019.

Net loss for the year ended December 31, 2020 was $102 $9 million for a loss per share of $2 77.

Compared to a net loss of $68 $3 million for $2 and <unk> loss per share for the comparable period in 2019.

Mark L. Jacobson: As a reminder, in Q3 of 2020, we secured a $225 million term loan facility with Hercules Capital, of which $175 million in funding remains available. This committed, non-dilutive capital gives us additional financial flexibility through the anticipated potential commercial launch. We believe our current cash position of $184 million, along with the remaining committed capital from our $225 million term loan facility, is sufficient to fund our anticipated operations based on our current operating plan into at least 2024.

As a reminder, and Q3 of 2020, we secured a $225 million term loan facility with Hercules capital of which $175 million and funding remains available. This committed non dilutive capital gives us additional financial flexibility through the anticipated potential commercial launches.

We believe our current cash position of $184 million, along with the remaining committed capital from our $225 million term loan facility is sufficient to fund our anticipated operations based on our current operating plan and to at least 2024.

Mark L. Jacobson: That concludes our fourth quarter 2020 financial review. I will now turn the call back to Mark to lead the Q&A. Thank you, Nick. Operator, may we please have our first question? Thank you very much. At this time, if anybody would like to ask a question, please press star one on your telephone keypad. Again, that would be star one on your telephone keypad. Your first question comes from Charles Duncan from Canter Fitzgerald. Your line is open. Hey, good morning, Ariel and team. Thanks for taking our questions. Yeah, a busy time for you.

That concludes our fourth quarter 2020 financial review I will now turn the call back to Mark to lead the Q&A discussion.

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

Thank you very much at this time, if anybody would like to ask a question. Please press star one on your telephone keypad, Okay and that would be star one on your telephone keypad and fresh question comes from Charles Duncan from Cantor Fitzgerald. Your line is open.

Hey, good morning, Ariel and team thanks for taking our questions. Yeah busy time for you congrats on the Ford motion and progress with low five.

Charles Cliff Duncan: Congratulations on the forward motion and progress with O5. I had a couple of quick questions with regard to the label, and I imagine you'll be talking about this more in terms of the claims that you were asking for with the 05 NDA. I guess I'm wondering would you anticipate the label to perhaps, the approved label to be explicit regarding the comment outcome or comment results with 1 in 2 failures in suicidal ideation, or would that just be data included in the label, and it would be a generalized MDD approval if granted?

Head and a couple of quick question with regard to the label and and I imagine you'll be talking about this more in terms of.

The claims that you were asking for was zero five N D. A I guess I'm wondering would you anticipate the label to perhaps and approved label to be explicit regarding the comment.

Outcome or comment results with one and two failures and suicidal ideation or would that just be data included in the label and it would be a generalized M D D.

Approval if granted.

Ariel: Good morning, Charles, and thanks for the question. So the label that we are targeting and that we have submitted the NDA for is treatment of major depressive disorder, MDD. And now our clinical trials, our controlled clinical trials, as well as our open label long-term studies, do include a broad range of patients who have MDD. And so we would not expect specific indications, for example, suicidal ideation, to be in the label.

Yes.

Good morning, Charles and thanks for the question.

So the label that we are targeting and and that we have submitted the NDA for the treatment of major depressive disorder M D D and the.

Now our clinical trial to Oregon, glaucoma trials as well as our open label long term studies do include a broad range of patients who have a M D D.

And so the we would not expect specific indications for example view suicidal ideation to be in the label and however, and Ah patients with M. D. D. Do you have suicidal ideation and patients for <unk> had been treated with.

Ariel: However, patients with MDD do have suicidal ideation, and patients with MDD have been treated with more than one prior treatment. So those data from the common trial that have been included in the NDE submission are data which certainly will be published and which we think will be very useful to clinicians, and we'll be able to make those data available to clinicians using our medical science liaison functions.

More than one prior treatments.

Data from the combo trial that had been included in the NDA submission and those are data, which are certainly will be published.

And which we think will be very useful to conditions, and we will be able to make those data available to clinicians.

And our medical science liaison and functions.

Charles Cliff Duncan: Okay, that makes sense. It should be useful for prescribers. Just sticking with 051, last quick question. Regarding the ACCORD study in Alzheimer's education, can you provide any additional color on how that study is going in terms of enrollment and what you anticipate the, call it, screen failure rate to be or the number of patients enrolled versus going on to the, I guess, the blinded portion and then being withdrawn?

Okay. Okay that makes sense should be useful for prescribers, just stick and whats 051.

Last quick question regarding the accord study and Alzheimer's agitation.

Can you provide any additional color on how that study is going in terms of enrollment and what you anticipate the coal at screen failure rate to be or the number of patients enrolled versus going onto the of I guess, a blinded portion and then and then being.

And withdrawn.

Yes.

Ariel: Those are great questions. It's early days in the study. So we launched the trial at the end of December. As you know, so it's very early days, especially for this type of study, whereby you do have this lead-in where everyone is treated with XSO5 in an open-label fashion, and then they're monitored not just for response, but for stable response prior to randomization. We'll have more to tell you and we'll be happy to share some of those observations and incorporate them into any kind of, Timing updates with regards to the

Those are great questions.

Early days and in the study so we launched the trial.

At the end of December.

As you know and so it's very early days, especially for this type of study whereby you do have this lead and where everyone is treated with <unk> five and an open label fashion and then they are monitored and not just for responsible for stable response prior to randomization will have more to tell you and.

And we will be happy to.

To share some of those obligations and incorporate them into.

And any kind of.

Timing updates with regards to the trial.

But right now it's too early.

Charles Cliff Duncan: Okay, last question regarding commercial. You mentioned the sales force sizing had been finalized, and I guess I'm wondering what you anticipate that sizing to be roughly, you know, not specifically, and then the breakdown of psych versus neuro focus, and how do you plan to accomplish that?

Okay last question regarding commercial you mentioned the sales force sizing.

And finalize and I guess I'm wondering what would you anticipate that sizing to be roughly you know not specifically and then the breakdown of psych versus narrow focus and and how do you plan to accomplish that.

Lori Englebert: Thanks, Charles, for the question. I'm going to turn it over to Lori.

Thanks, Charles for the question and I'm going to turn it over to Laurie.

Lori Englebert: Hey Charles, thanks for the question. I think you probably will not be surprised if we tell you we're not going to tell you the exact size of the sales force, but what I can tell you is that we are highly confident that the size that we have anticipated will cover the number of physicians that will be high prescribers of AXSR5. And we do believe that our digital-centric commercialization approach will be able to provide information to physicians when they need it, how they want it, and at the time that they want it.

Thanks, and thanks for the question.

I think you probably will not be surprised if we tell you we're not going to tell you. The exact size of the sales force, but what I can tell you is that we are a highly.

Highly confident that the size that we have anticipated will cover the amount of physicians that.

Will be high prescribers of access for five and we do believe that our digital centric commercialization approach will be able to provide.

Information to physicians when they need it and how they want it and time that they want it and I think that's really important to understand because our promotion is not just personnel and there will be a large component of non personal promotion as well.

Lori Englebert: And I think that's really important to understand because our promotion is not just personal. There will be a large component of non-personal promotion as well. And regarding your question around 07 and that launch, Look, everything we're doing in preparation for the O5 launch is working under the assumption that O7 will follow very closely after. So all of the structures that we're putting into place, Salesforce, and digital, will all be readily capable of scaling at the time of launch for O7.

And.

And regarding your question around a seven and and that launch.

And everything we're doing.

And preparation for the <unk> five launch is working under the assumption that aside and we'll follow very closely after so all of the.

Structures that we're putting into place sales force.

Digital will all be readily capable of scaling at the time of launch for a seven.

Charles Cliff Duncan: Okay, that's helpful. Thanks, Lori and Ariel, for the added color.

Okay. That's helpful. Thanks, Laurie and aerial for the added color and should be effective looking forward to the progress this year.

Mark Goodman: It should be effective. I'm looking forward to the progress this year. Your next question will come from Mark Goodman from SVB Larynx. Your line is open. Yes, good morning.

Thank you.

Your next question will come from Marc Goodman from SBB Leerink. Your line is open.

Yes, good morning.

Ariel: I understand you're not going to give us the number of reps, but can you give us a sense of the spend that you're going to do this year? Maybe some type of spending guidance, specifically for SG&A, is what I was focused on. Second, can you just give us a sense of the payer discussions so far for depression and how those are going, and how they are appreciating the differentiation, the new mechanism? I'm just curious how that's going.

Understand you're not going to give us the number of reps, but can you give us a sense of the.

And the spend that youre going to do this year and maybe some type of spending guidance.

Specifically for SG&A is what I was focused on <unk>.

And second.

Can you just give us a sense of the payer discussions so far for depression, and how those are going and.

And how they are appreciating the differentiation and the new mechanism just curious how that's going and then third.

Ariel: And then third, just curious about fibromyalgia. You're going to meet with FDA. Can you talk about the different scenarios if they come back and say, okay, you can file with what you have? Are you prepared to file and then move forward and market this product on your own? Are you thinking about potentially partnering it, just because it's such a large indication? And if they say to do another study, are you prepared to start another study before the end of the year?

Just curious on the fibromyalgia and youre going to meet with FDA.

Can you talk about the different scenarios, if they come back and say Okay. You can file with what you have are you prepared to file and then.

Move forward and market this product on your own or are you thinking about potentially partnering it just because it's such a.

A large indication and if they say to another study prepared to start another study before the end of the year.

Ariel: Thanks for the multi-part questions there. So I'll take the fibromyalgia question first, and then I'll turn it over to Nick and to Lori for the other questions on spend and payer discussions. With regard to fibromyalgia, we're looking forward to our FDA meeting, which is scheduled in the second quarter to discuss the development path forward for that product candidate. This will be our first meeting with the FDA since we've gotten the data.

Thanks for the.

Multipart questions there so.

And so.

So I'll take the fibromyalgia question first and then I'll turn it over to Nick.

And then Laurie for for the other questions on.

And on spend and and.

Payer discussions.

With regards to fibromyalgia and we're looking forward to our FDA meeting, which is scheduled and the second quarter to discuss the development path forward for that product candidate and this will be our first meeting with the FDA.

And we've gotten the data. So we will have a lot more to tell you and hopefully once we have that meeting and as a reminder.

Ariel: So we'll have a lot more to tell you, hopefully, once we have that meeting. As a reminder, there are two studies, two efficacy trials, which were controlled trials, that have been completed and which were positive. So that puts us in a very good position.

There are two studies two efficacy trial for controlled trials.

We have been completed and.

And which were positive so that puts us and a very good position.

Ariel: In the theoretical scenario where, let's say, there was absolutely nothing more that we had to do from a clinical perspective, we would still need to manufacture commercial supplies. And what I can tell you is that work is already underway to make sure that we can manufacture the product. This is a novel chemical entity. And so, therefore, there's been a lot of work that our CMC team has been doing in order to synthesize it. So, that work is well underway, and is progressing well. I'll turn it over to Nick to answer your first question.

And the theoretical under the theoretical scenario, where lets say it was absolutely nothing more than that we had to do.

From a clinical perspective, we would still need to.

Manufacture commercial supplies.

And what I can tell you is that work is already underway to make sure of that.

We can manufacture the product this is.

And novel.

Chemical entity and so therefore.

And there's been a lot of work that our CMC team has been doing in order to want to synthesize. It. So that work is well underway and is progressing well.

Nick Pizzie: Thanks, Herriot. Thanks, Mark, for the question.

I'll turn it over to Nick.

Nick Pizzie: As you know, we don't necessarily give expense guidance, but I can give a little bit of guidance on the cash runway. As a reminder, we had $184 million in cash at year-end. We additionally have the $225 million debt facility. So, you know, I feel like we're in a really strong position from our financial resource base. The cash runaway, so you're aware, this takes us into at least 2024 based on our current operating plan and includes all launch readiness, all launch expenses, including the field force for AXS 05 and AXS 07, also includes funding for the second phase three Alzheimer's agitation trial So the runway currently, you know, just in conclusion, takes us through both potential launches upon NDA approval for both NDD as well as the acute treatment of migraines.

For your first question. Thanks, Terry Thanks, Thanks, Mark for the question as you know, we don't give necessarily expense guidance, if I could get a little bit of guidance on the cash runway.

As a reminder, we had $184 million and cash at year and we are.

Additionally, have the $225 million debt facility.

So feel like we're in a really strong position and from a financial resource base.

The cash for our way so youre aware of this takes us into at least 2020 for based on our current operating plan and <unk>.

<unk> all launch readiness launch expenses.

Including field force for access of five and <unk> seven.

Also includes funding for the second phase III Alzheimers agitation trial, a continuation of the merit trial for CRD and soon to be started.

And <unk> 12 trial and narcolepsy.

So the runway currently.

Just in conclusion takes us through both potential launches upon NDA approval for both and D D as well as the acute treatment of migraine.

Lori Englebert: Hey, and I'll quickly answer the payer question. So I think we all know, depression is the number one cause of disability worldwide. And the prevalence of depression is just continuing to grow, especially with the pandemic. You know, sometimes we hear to the tune of three X.

Okay and.

I'll quickly answer the payer the payer question so.

I think we all know depression as the number one cost and disability and worldwide and the prevalence of depression, and there's just continuing to grow, especially with the pandemic and sometimes too we've heard to the tune of three X.

Lori Englebert: So payers are paying attention, right? Depressed patients cost money and they are acutely aware of the... The other clinical profiles of products that are already on the market. When we discuss with payers and what we've seen in early discussions, Yes, bringing forth a novel mechanism of action that's patient friendly and, you know, reminding them that this will be the first one in 60 years is interesting to them, very interesting to them, but what really sticks out is our clinical profile. So our data is highly differentiated versus the other products on the market, and what I believe we've heard, and again, in early discussions, what attracts them most is the

So payers are paying attention right and depressed patients cost money.

And they are acutely aware of the.

The other clinical profiles are products that are already on the market when we discuss with payers and and what we've seen and in early discussions.

Yes, bringing forth a novel mechanism of action that is patient friendly and reminding them that this will be the first one and 60 years is interesting to them are very interesting for them.

But what really sticks out is our clinical profile. So our data is highly differentiated versus the other products on the market and what I believe we've heard and and again and early discussions what attracts them most.

The rapid onset of share of our mission and the durability that we show and the product.

Joon So Lee: And your next question comes from Joon Lee from Truist Security. Your line is open.

And your next question comes from Joe Joon Lee from <unk> Securities. Your line is open.

Ariel: Hi, thanks for taking our questions and thanks for the update. So following up on the, you know, peer discussion and your mention of the rise and prevalence of depression, I wanted to follow up on that. In one of your slides, you note an increase in the prevalence of depression from 22 million, you know, pre-pandemic to 71 million during the pandemic, more than 3x increase in prevalence. Unfortunately, you've already completed your phase three, but if you were to conduct a phase three trial today, would you do anything differently? You know, what I'm trying to understand is whether it is similar in other countries, maybe, maybe. I just would love to hear your thoughts there. Thank you.

Hi, Thanks for taking our questions and thanks for the updates so following up on the payer discussion and that you know you mentioned thats right and prevalence of depression.

Wanted to follow up on that and.

One of your slides you know increase and the prevalence the question from $22 million pre pandemic to 70 71 million during the pandemic more than <unk> increase in tablets and unfortunately, you've already completed your phase III, but if you want to conduct the phase III trial today.

Would you do anything differently, what I'm trying to understand this.

The new cases that the question.

And the pandemic are quantified mbd or something more multi factorial and nature and acute would've needed to and Ah.

Upsized and steady or something like that to suppress noise and that this phenomenon unique for U S or.

And similar in other countries maybe.

And maybe.

And just would love to hear your thoughts there. Thank you.

Ariel: Thanks, Joon, for the question. I mean, there is a lot of theoretical stuff there.

Yes, thanks for the question and a lot of theoretical there.

Ariel: But I think you do raise some interesting questions. So from a public health perspective, it's very clear the effect of the pandemic on mental health and also on depressive symptoms. It's been very well documented, I think, definitely in some high-profile journals by some well-respected clinicians. A Significant Increase in Depressive Symptoms, and Lori can maybe speak to this a little bit, but we've started to also see that, you know, work its way into prescription trends.

But.

I think you do raise rates from interesting questions.

From a public health perspective, it's very clear.

The effect of the pandemic on.

Mental health and.

And also one on depressive symptoms, it's been very well documented and I think definitely and some high profile journals.

And by some some well respected our clinicians so the data are clear there.

There is.

A significant increase and depressive symptoms and.

Lori you can maybe speak to this a little bit but we.

We're starting to also see that.

Work its way into.

Prescription trends.

Ariel: Now, so what that means is there's an acute need to treat patients, and also, there's a great opportunity for companies that can provide novel mechanisms of action that will work quickly to help these patients. So that's on the clinical need side of things. Now, from a clinical trial conduct perspective, I think that you do bring up an interesting point that there is an unknown there, and that unknown is what impact the pandemic and, you know, the mental illness from a pandemic could potentially have on being able to test your drug to see if it works. That's a theoretical and, you know, we can't really say too much about that.

And now.

So what that means is there's acute need.

To treat patients and and.

And also there's a great opportunity for <unk>.

Companies that can provide novel mechanisms of action.

And that will work quickly that will help.

And these patients.

So that's on the clinical need side of things now.

Now from a clinical trial conduct perspective.

I think that debt.

And you do bring up and interesting point that there is an unknown there.

And then and known as what impact.

And with the pandemic and.

With the mental illness from a pandemic have potentially on.

On being able to to test your drug to see.

If it works.

And that's a theoretical.

And we so we can't really say too much about that.

Ariel: One of the things that we did was to look at the impact of AXS05 during the pandemic through our long-term open-label safety extension trial. And so we were very interested to see, you know, what the impact was. Our drug, you know, would affect patients with their depressive symptoms. In the context of the pandemic, and we can only speak to our data, and what we showed, as you know, and what we reported was very profound reductions in depressive symptoms, incredibly high rates of response and remission that either were maintained or increased over the 12-month treatment.

One of the things that we did do was.

To look at the impact of <unk> five during the pandemic through our long term open label safety extension trial and until we were very interested to see what what impact.

Our drug would have on patients and their depressive symptoms.

And the context of the pandemic and and we can only speak to our data and what would we showed as you know and what we reported was.

Very profound reductions in depressive symptoms incredibly high rates of response and remission.

That either were maintained or increased over the 12 month treatment period.

Joseph John: Fantastic. Thank you. Your next question comes from Joseph Thum from... Call when in the company. Your line is open.

Fantastic. Thank you.

And your next question comes from Joseph Feldman from.

Cowen and company your line is open.

Ariel: Hi there, thank you for taking my question. A little bit on the comment data, in those subset data, was there anything that surprised you in terms of response in any of the individual subsets? And maybe in terms of positioning upon launch, is there anything that your MSL team is doing to position the therapy in a certain subset of patients that will be maybe more early adopters? And then, related to that, does the subset data give you any read through into your expectations for merit later this year?

Hi, there. Thank you for taking my question a.

A little bit on the comet data and those types of data or was there anything that surprised you in terms of response and in any of the individual subsets.

And maybe in terms of positioning upon launch.

And the MSL team is doing to position that therapy, and a certain subset of patients that would be maybe more early adopters.

And then finally related to that does the subset data give you any read through into your expectations for Merit later this year.

Ariel: So, thanks for the question. In terms of points that were surprising in the data, I think it was good to see that the rapid onset of action and the significant percentages of patients achieving remission and response that we saw in the control trials were replicated in the COMET data. One of the sub-studies that we were really interested in was the suicidal ideation sub-study. A small number of patients, but as you can imagine, rapid onset of action is really important for that symptom and in those patients, and what we saw was that there was a resolution of suicidal ideation in that subgroup in 60 percent of the patients at week one, and that only increased to the vast majority of patients after two weeks

So thanks for the question.

And in terms of.

In terms of.

Points that were surprising and.

And the data.

Hi.

And I think we it was good to see that debt.

The rapid onset of action and and.

The significant.

Percentages of patients achieving remission and response that we saw and the control trials.

For replicated in the common data one of the the.

One of the subsidies that we were really interested and was the suicidal ideation sub study small number of patients, but as you can imagine rapid onset of action is really important.

And for that symptom and and in those patients and and what we saw was that.

And there was a resolution of suicidal ideation and that the med sub group and 60% of the patients at week, one and that'll lead.

Increased to the vast majority of patients after two weeks so flat.

Ariel: So that was definitely interesting, and number two on the list was the fact that the efficacy that we saw in the controlled trials did translate also to patients who had failed two prior treatments, so patients who are traditionally referred to as treatment-resistant depression patients. So it was really good to see that in a real-world setting as it relates to expectations and as it relates to what implications that would have for the merit study.

That was.

And really interesting and and I think.

Number two one and the list was the fact that.

The efficacy that we saw and the controlled trials.

Translate also to patients who had failed two prior treatments for patients who are traditionally referred to as treatment resistant depression patients. So why it was really good to see that and and.

And real world setting.

And as it relates to expectations.

As it relates to what implications that would have for the the merit study.

Ariel: Those points, those observations can only be positive in terms of the profile of the product, and we've never done a randomized withdrawal study design before, so it'll be interesting to see what those show, and that's the... benefit, and one of the reasons why you conduct phase two trials. So we're looking forward to seeing how the product performs in that setting, and then I'm going to turn it over to Cedric to talk about MSL Strategies.

Yes.

And those points of those observations can only be positive in terms of.

The profile of the product and we've never done and randomized withdrawal study design.

For so it'll be interesting to see.

And what those show and and that's the.

Benefit and one of the reasons why you conduct phase two trials and so we're looking forward.

<unk> seen how the product performs in that setting.

And and and I'm going to turn it over to Cedric to talk about.

MSL strategies.

Yes, Thanks, Ariel and I would just say that.

These data from comment or very exciting I mean in terms of.

The response and mattress for mission.

Madras and also the fact that and translates into clinically observable response, and remission rates and that this was clear across the overall comment as well as those who have.

Cedric O'Gorman: Yeah, thanks, Herriot. I would just say that, you know, these data from Comet are very exciting, I mean, in terms of,,,,,,,, So the MSLs have these data in hand, we've been out talking to key opinion leaders getting their insights on the data, it's been a great [inaudible] Goodman, David Amsellem, Vikram Pur Thank you so much. Your next question will come from Myles Minter, on behalf of William Blair.

Failed to respond to to antidepressants and their current episode and suicidal ideation and so the MSL and have these data in hand, we have been talking to key opinion leaders getting their insights on the data that's been a great recipe.

Crescent activity to it and excitement about the new mechanism of action and I think that what's important from comet is not only are you seeing these responses early on but theyre being sustained and with really sort of impressive.

Compliance and maintenance with treatment for up to 12 months. So that's what's really exciting is that the drug appears to be working but also patients who are willing to stay on it for.

And for the long term so the msos are out there right now.

Insights and talking about these data and we will be presenting data at upcoming conferences as well.

Excellent. Thank you so much.

Okay.

Your next question will come from Myles Minter from William Blair. Your line is open.

Cedric O'Gorman: Your line is open. Hi everyone, thanks for taking the questions. I'm just wondering from the payer perspective whether you've sort of engaged in the conversations regarding where 05 might actually sit in the treatment paradigm from their perspective and whether the DCC platform that you're running on the commercial front is actually touching base with the appropriate prescribing physicians that are seeing patients, say, with two or more prior failed antidepressants.

Hi, everyone and thanks for taking the questions.

Just wondering from the pilot perspective, whether you sort of engaged and the conversations regarding words, you are five not actually sitting in the treatment paradigm from their perspective and.

Whether it's the same day.

Platform that you're running on the commercial front, whether thats actually touching base with the appropriate prescribing.

Physicians that are same patient sire with slight two or more prior filed antidepressants.

Myles Robert Minter: Ahem. Hey Myles, thanks for the question. I think it's a little bit too early for us to know where the payer discussions are going to net out, so answering your first question, It was difficult at the time. We are, as I mentioned earlier, very encouraged by those discussions that we are having right now. They seem to respond very well to our clinical data package that we're putting together. In terms of the DCC approach, I'm not quite sure I understand or have understood your question correctly. Could you repeat that? Would you mind repeating it?

Okay.

Hey, Myles thanks, and thanks for the question.

It's a little bit too early for us to know.

For the payer discussions are going to net out there and so answering your first question.

Difficult at this time, we do.

As I mentioned earlier, we are very encouraged by those discussions that we're having right now.

And they seem to respond very well try and clinical and preclinical data package that we were putting in front of them.

And turning to the DCC approach.

And I'm not quite sure I understand are understood. Your question correctly could you could you repeat it and would you mind repeating it.

Yes, I'm just wondering like.

Myles Robert Minter: Yeah, I'm just wondering, like, with the target for that platform and also for your sales force, what the breakdown of patients that have failed two or more prior therapies would be at those target accounts and, you know, that are classified as TRD patients versus standard MDD.

With the target prescribing accounts for that platform and also for your sales force.

And what the breakdown of patients that have failed so we'll more prior therapies.

Target accounts and that of course hottest payout a patients versus standard MTA day.

Yes, yes.

Ariel: Yeah, I think I understand your question. Yeah, so I'll turn it over, I'll turn it back to Lori, but I just wanted to point out that the data are pretty clear that, you know, roughly two-thirds or more of patients already fail or respond inadequately to at least one priority.

And I understand your question.

Yes.

I'll turn it over and I'll turn it back for it tomorrow, but I just wanted to just point out that.

The data are pretty clear that you know roughly two thirds or more of patients.

Already fail or respond and adequately.

And to at least one prior treatment for it.

Lori Englebert: Yeah, I agree. You know, the majority of our target physicians are high prescribers, so the likelihood that they're treating patients who have failed one or more is really high.

And I agree.

Majority of our target physicians are high prescribing physicians and so the likelihood that they are treating patients who have failed one or more.

It is really high.

Okay Cool and then maybe on zero seven.

Myles Robert Minter: Okay, cool. And then maybe on 07.., and then the movement trial data looks really good from my perspective. If you've given any updates as to the frequency of dosing for patients out to 12 months, and also, were those patients treated at the earliest signs of migraine, like an intercept, or at confirmed migraine, like in momentum?

And then moving and Chile debt.

It's really good for my perspective, if you can give you and any updates as to the frequency of dosing.

And for patients out to 12 months.

And also with those patients traded at the earliest signs of micron and locking intersect ore and spend.

And Mike Ryan and locking momentum.

Amanda Jones: Thanks for the question, Myles. I'm going to turn it over to Amanda.

Thanks for the quick question, Myles and I'm going to turn it over to Amanda.

For the movement study and the patients were allowed to treat.

Amanda Jones: Hi Myles, for the movement study, the patients were allowed to treat themselves at any point in time following the onset of migraine pain, so it really reflects more of the real world data and real world use of the drug and also the data that was captured during the Momentum and Intercept trials.

And at any point in time, following the onset of migraine pain. So it really reflects.

For the real World.

Data and <unk>.

Use of the drug and also the <unk>.

Data that was captured during the momentum and intercept trials.

Vamil Devan: Okay, cool. Thanks for the questions. Your next question will come from Vamil Devan from Michoac. Your line is open. Hey guys, this is Await for Obama.

Okay cool thanks for the questions.

Your next question will come from that mill and David <unk> from Mizuho. Your line is open.

Hey, guys, Thanks, and don't wait for Obama.

Ariel: Um, just a couple of questions on AXS07. Just wondering, um, why the pushback on 2Q learnings and 2Qs filing? But it's the same issue that was, um, was previously discussed or something that's different. And secondly, on just thinking about pricing ahead, just wondering how you're thinking about pricing for XS05 in MDD, but you know, you will also have agitation, and the pricing there could be different, and just wondering how you are approaching this and how you are, I guess. Deep discussion with payers might be going on. Thanks.

Just a couple of questions on <unk> seven and just wondering.

Why the push back to two key learnings.

Qs filing.

And the same issue that was and <unk>.

As previously discussed or something that's different and.

And secondly.

And just thinking about pricing ahead.

And wondering how you're thinking about pricing for excess Oh five.

And in M D D.

And you will also have agitation and the pricing there could be yes.

Yeah, Frank and just wondering how you are approaching this.

And how your I guess.

Deep discussion with payers might be going.

Ariel: Thanks for the question. With regard to 07 and the NDA filing, the team remains on track to complete the filing by the end of the quarter.

Thanks.

Right.

Great. Thanks.

Thanks for the question with regards to <unk>.

And the NDA filing and the team remains on track to complete the <unk>.

Finally, and by the end of the quarter. However, we are waiting on one vendor report, which will slip into the very beginning of the second quarter and and Thats. The reason.

Ariel: However, we are waiting on one.

Ariel: Vendor Report, which will slip into the very beginning of the second quarter, and that's the reason behind the adjustment there in guidance.

And behind the adjustment there and guidance and.

Lori Englebert: Hi, thanks for the question. Regarding pricing, so whenever you approach pricing discussions with payers, typically, companies focus on fair and timely access, and a large portion of that will be associated with where you price. But the balance of that is we need to price for the value that the product brings, and so we're working through that right now to make sure that we understand how we should appropriately price to represent what value we're bringing to the market.

Laurie Thank you.

Hi, and thanks for the question regarding pricing so whenever you approach pricing discussions with payers typically accompanies.

Focus on fair and timely access and all.

And a large portion of that will be associated with where your price, but the balance of that and we need to price for the value that product brings and.

And so we're working through that right now and to make sure and and we understand how.

And how we appropriately price to represent and what value, we're bringing to the market.

Lori Englebert: And then Lori just worked through the AD agitation. Yeah, and that encompasses...

And then we're just towards the worst at the 80 agitation yes.

Net income for the ADP agitation piece of it.

Lori Englebert: Yeah, and that encompasses the AD agitation piece as well.

Okay. Thanks.

And your next question will come from Matt Kaplan from Ladenburg Thalmann. Your line is open.

Matthew Lee Kaplan: Okay, thanks. And your next question will come from Matt Kaplan from Luttenberg Feldman. Your line is open. Hi, Herriot and everyone else. I want to congratulate you on the progress during the quarter. Can you give us a sense now that you've submitted the AXS 05 MDA, I guess given the breakthrough designation you have in MDD, what are your expectations for a potential priority review?

Hi, good morning, and right now.

Good morning, Matt and everyone else.

Want to congratulate you on the progress during the quarter.

Can you give us a.

A sense now that you've submitted the access so far and da I guess, given the breakthrough designation and Havent and M. D. What are your expectations for a potential priority review.

Ariel: So, as you mentioned, we do have breakthrough therapy designation for the product, and we do believe that we qualify for priority review, which is a six-month review. However, that is a determination that is made by the FDA. And the way that it works is that priority review is not automatic, and at the time of the NDA filing, you do request priority review, and it is a determination that is made and communicated to the company upon the FDA's decision of whether or not to file the application. So our plans with regard to launch, et cetera, they're predicated on, they assume a six month review. But again, that is really up to the FDA.

So.

As you mentioned, we do have breakthrough therapy designation for the product.

And we do believe that we qualify for priority review, which is six month review however.

And that is a determination, which is made by the FDA and the way that it works is that a priority review is not automatic.

And at the time of the NDA filing and you do request priority review.

And it is a determination which is made and communicated.

Two two the company upon the Fda's decision of whether or not to file the application.

So so our.

Our plans with regards to launch et cetera, they're predicated they assume a six month review, but again.

Matthew Lee Kaplan: Okay, helpful. And then in terms of AXSOS 7, I guess we focused a bit on the commercial prep for 05 already. But I guess, maybe more for Lori, where are you in the preparation in terms of the research you're doing and payor interaction for 07, given I guess it's kind of the near term, near term NDA filing there?

That is really up to the FDA.

Okay helpful and then in terms of and excess of seven and I guess, we focused.

A bit on the commercial prep on O five already.

And maybe more for Lori.

What are what is what.

And what where are you and the preparation in terms of research you're doing and.

Payer interaction for.

For O seven given I guess, that's kind of the near term near term NDA filing there.

Lori Englebert: Regarding O7, as I mentioned earlier, we have always anticipated that O7 would follow very closely behind O5 in terms of launch, and therefore, we've actually been preparing on all fronts to have a staggered approach but scalable if we were to receive approval for AXS O7. In terms of payer negotiations, exactly, we have performed market research but have not started the 07 payer discussions just yet.

Yeah, Hey, Thanks, Matt for the question.

Regarding our seven as I mentioned earlier, we have always anticipated that I said and went to follow very closely behind a five in terms of launch.

And therefore, we've actually been preparing on all fronts to have a staggered.

Approach, but scalable.

And we were to receive approval for HSI seven.

In terms of payer negotiations exactly we have performed.

And market research, but have not started that.

Seven payer discussions just yet.

Matthew Lee Kaplan: Okay, very good. And then last question, in terms of Aereo, you mentioned you're on track to start phase three for AXS-12, narcolepsy, and cataplexy next quarter. Can you give us a sense of what your thinking is in terms of the design of that trial and kind of timeline to completion, potentially?

Okay.

And then last question in terms of <unk>, you mentioned, you're on track to start the phase III and current excess of 12 X 12 excess 12.

And narcolepsy cataplexy.

And next quarter can you give us a sense of what youre thinking and in terms of the design of that trial and and.

And.

Kind of timelines for completion potentially.

Ariel: So with regard to the trial design, it will be a parallel group design. So it'll be similar in some ways to the phase 2 trial which we conducted, except the phase 2 trial was a crossover design. This will be a parallel group design.

So.

With regards to the trial design, but it will be a parallel group design so it'll be.

Similar in some ways too.

And the phase two trial, which we conducted except for phase two trial was a crossover design and this will be a parallel group design. So we expect we would expect to.

Ariel: So we would expect to randomize subjects to AXS12 and to placebo. And then, with regard to expectations around how long it would take to enroll a study, you know, once we start the study, we'll provide you details with regard to the size of the study, and that, of course, will determine potentially how fast. It could enroll. One of the things that we can point to are the metrics around the Phase II enrollment. As a reminder, that was a 21-patient study that was conducted at roughly 12 sites and that enrolled in approximately.

Randomized subjects to excess 12.

And and to placebo and then with regards to.

And our expectations around how long it would take to enroll the study.

And once we start the study we will provide you details with regards to the size of the study and that of course, we will.

We will determine and potentially how fast.

It could enroll.

And one of things that we can point to you and where the metrics around the.

The phase two enrollment.

Minder that was.

A 21 patient study.

Which was conducted at roughly 12 sites and.

And that.

And rolled.

And and approximately six months.

Vikram Purohit: Thanks for the added detail. The next question will come from Vikram. Purohit, from Morgan Stanley, your line is open.

Great. Thanks.

Thanks for the added detail.

Your next question will come from debt Cran.

From Morgan Stanley Your line is open.

Ariel: Great, thanks for taking my question. I just had one on AXS05 for smoking cessation. So I see in your release that you have an FDA meeting scheduled here for the third quarter. I just wanted to see what you're looking to learn from your meeting with the FDA here and what you think an eventual subsequent pivotal study in this indication could look like.

Yes.

Great. Thanks for taking my question.

Just had one on excess of five for smoking cessation. So I see in your release that you have and FDA meeting scheduled here for the third quarter and just wanted to see where youre looking to learn from and meeting with the FDA here and what you think.

And eventual subsequent pivotal study and this indication could look like.

Ariel: So thanks for the question. We're very excited about smoking cessation. And, you know, on the back of the positive phase two data from a small study, we're looking to meet with the FDA to figure out what an efficacy trial would look like. So the phase two study did look at smoking behavior, but that is not a registration endpoint. Certainly, it was very helpful for signal detection, which we saw. And so what we're going to be looking to get out of that meeting is guidance and agreement on the design of the next study, which would be an efficacy trial. So we're very much looking forward to those discussions. In registration trials in smoking cessation, typically, the end point is abstinence. So that is what we would expect from the next study.

So thanks for the question.

We're excited about our smoking cessation.

And on.

On the back of the positive.

Phase two data.

And from a small study, where we're looking to meet with the FDA to figure out.

What an efficacy trial would look like so the phase II study did look at smoking behavior, but that is not a registration endpoint certainly.

It was very helpful for signal detection.

We saw and the so we're going to be looking.

To get out of that meeting is.

Guidance and agreement on the design of the next study, which would be and efficacy trial.

So for one.

And we're very much looking forward to.

For those discussions.

Registration trials and smoking cessation and typically the endpoint is.

As abstinence.

So.

So that is what we would expect for the next study.

Chris Howerton: Okay, got it, thank you. And your next question will come from Chris Howerton from Jefferies. Your line is open. Hi, good morning. Appreciate you taking the time to ask the questions. Congratulations. So I guess most of them have been asked at this point, but I guess for O5, with respect to Alzheimer's disease agitation, there's a possibility that we're going to get increased competition within that space over the next couple of years with a variety of companies developing therapeutics there. So, I guess, how do you see O5 competing in this landscape? Particularly, obviously, as we all know, safety is the key concern for this patient population.

Okay got it thank you.

And your next question will come from Chris Howerton from Jefferies. Your line is open.

Hi, good morning.

Appreciate you, taking the time and the questions congratulations.

So I guess most of US had been been asked at this point, but I guess for <unk>.

With respect to Alzheimer's disease agitation.

There is a possibility and we're going to get increased competition within that space over the next couple of years with a variety of companies developing therapeutics. There. So I guess how is it that you see oh five competing in this landscape.

Particularly obviously as we all know safety is a key concern for this patient population. Thank you.

Ariel: Thanks for the question. It's a very interesting and serious disease area. The term unmet medical need gets thrown around quite a bit, but here, this would be a good descript proxy. Yeah, yeah, it'd be Yeah, so you're talking about a disease where there is currently no product that is approved, and the drugs that are used off label have black box warnings against their use in that specific patient population. And yet, clinicians do need to treat these patients because of the seriousness of the condition. So, um, so right now, there's nothing approved.

Thanks for the question.

It is.

It's a very.

Your interesting and I'm serious.

Disease area.

The term unmet medical need gets thrown around quite a bit but here you.

This would be.

Good.

Good day Fox, Yeah, Yeah, it'd be yeah, so youre talking about.

The disease, where we're there currently is no product that is approved and the drugs that are used off label.

Black box warnings against their use in that specific patient population.

And yet.

And clinicians do need to treat these patients because of the seriousness of the condition. So for.

Right now there and there's nothing approved so from a confirmed for me and a competitive perspective. So it really all depends on the clinical data, it's very difficult for us to comment on drugs that are in development. We know that this is an area.

Ariel: From a competitive perspective, it really all depends on the clinical data. It's very difficult for us to comment on drugs that are in development. We know that this is an area that has not been kind to drug development.

And that has not been kind to drug development.

Ariel: And, you know, we're very fortunate that we have one pivotal trial that is positive that did show really good efficacy, which was rapid, but also really good safety. So the drug was incredibly well tolerated in the advanced phase 1 trial. And so we're looking forward to enrolling and completing the ACCORD study. And with regard to just further products that are in development, one thing that I would say is that it shows that there is just a significant clinical need. And it would be great to have numerous products that are available to treat these patients given the seriousness of the condition and positive data from other companies.

And and we're very fortunate that we have one pivotal trial.

That is positive but did show.

Really good efficacy, which was rapid but also a really good safety, so the drums and incredibly well tolerated and the advance one trial and and so we're looking forward to.

Two enrolling it and and completing the accord study.

And with regards to just further too.

Other products that are in development and one thing that I would say is that it shows that.

That there is a.

A significant clinical need and and you know it.

It'd be great to have numerous products that are available to treat these patients given the serious the seriousness of the condition.

But it's.

Yatin Suneja: Okay. All right. Well, thank you, Ariel. I appreciate it. And I also look forward to that as well, and your next question will come from Yatin Suneja from Guggenheim. Your line is open. Hey guys, this is Eddie from Forgotten. Thanks for taking my question. So just to follow up on TRD, can you, given what you saw in Stride and then recently with the Comet study, can you give us an update on sort of what the development path looks like and the timelines to get to an SNDA and TRD, and how will the merit data coming later this year sort of influence that path? Thanks so much.

It's impossible to comment on when and theoretically when we've not seen.

Positive data from other companies.

Okay Alright.

Thank you and I appreciate it and I also look forward to that as well. Thanks. Thank you.

And your next question will come from Yadkin and <unk> from Guggenheim. Your line is open.

Hey, guys. This is Eddie on for yacht and thanks for taking my questions. So just a follow up on CRD can you given what you saw and stride and then recently with the Comet studies can you give us an update on for what the development path looks like and the timelines to get to and SMB and CRD and how will the merit Dana coming later this year sort of influence that Todd. Thanks, So much.

Ariel: The indication that we filed is MDD, and so that's the broadest indication. It encompasses the entire spectrum of major depressive disorder. So we're very happy with that indication should we be successful with the MDD review, and we do not intend to conduct another phase three trial in treatment-resistant depression. What we have done is to generate data that will help clinicians to understand how the product performs in a wide range of patients with major depressive disorder, including patients who have failed two prior treatments.

And the indication that we filed.

M D D and so thats the broadest indications that encompasses.

And the entire spectrum of major depressive disorder. So so so we're very happy with that that indication should we be successful.

The NDA review and.

And we do not intend to conduct and.

Another phase III trial and treatment resistant depression.

What do we.

What we have done and and.

Is to generate data that will help clinicians to understand how the product performs in a wide range of patients with major depressive disorder, including patients who have failed two prior treatments.

Ariel: So from that perspective, we're very happy that the SCRIDE study was conducted. We think that the Comet TRD data does provide very helpful information to clinicians in a real-world perspective, and we think that the MERIT study may also provide data that will be useful to clinicians, again, in the right setting, that is, in a scientific setting.

So from that perspective, we're very happy that the described study was conducted.

We think that the common tier day data.

Does provide.

Very helpful information to clinicians and our real World perspective.

And and we think that the Merit study.

May also provide data that will be useful to clinicians again, and the right setting, but it isn't a scientific study.

Raghuram Selvaraju: Great, thank you so much. We have time for just a few more questions, and we'll try to get through as many as possible. Your next question is from Ram Selvaraju from H.C. Wainwright. Your line is open. Thank you so much for taking my questions. And I wanted to ask about the general allocation of sales and marketing commercialization resources across the different indications for AXS05 as you look towards the possibility of this drug potentially being a triple or even a potential quadruple threat in the CNS neuropsych space.

Great. Thank you so much.

We have time for just a few more questions and we'll try to get through and spending as possible and your next question is from Ram <unk> from H C. Wainwright. Your line is open.

Thank you so much for taking my questions and I wanted to ask about the general allocation of sales and marketing and commercialization resources across the different indications for access so five.

As you look toward the possibility if this drug potentially being.

Triple or even a potential quadruple threat in the CNS neuroscience space and.

Raghuram Selvaraju: And in particular, if you could talk through how you anticipate the different sales and marketing strategies to be taken with AXS05 effectively being deployed, and if you can especially describe any particular initiatives that are likely to be aimed at specific types of institutions with the aim of optimizing the commercial value of this product.

And in particular, if you could talk through how you anticipate the different sales and marketing strategies to be taken with a excess of five.

And effectively being deployed and if you can.

Specially describe any particular initiatives that are likely to be aimed at specific types of institutions with the aim of optimizing the commercial value of this product.

Raghuram Selvaraju: Thanks Ron for the question; I'll turn it over to Lori, but you do raise some interesting questions which we've certainly thought about as a team with regard to the potential different indications for AXS 05.

Thanks, Rob for the question and I'll turn it over to Laurie.

But you do raise.

Some interesting.

<unk>, which we certainly thought about.

As a team with regards to the potential different indications for.

Lori Englebert: Yeah, hey, Ram. Thanks for the question. It's a little bit difficult question to answer at this point in time. You know, AD agitation, we need to see how the trial finalizes, but we are absolutely always thinking about how we leverage the sales force, when we leverage the sales force, and what that overlap of positions might look like. Again, you know, as we built our sales force sizing, design, and structure, we did that with the understanding that we would have follow-on indications coming in particularly different disease areas and also different treating physicians. So we've made great efforts to ensure that there's efficiency there if that were to happen.

For excess of five yeah, Hey, Ron Thanks for thanks for the question.

A little bit difficult question to answer at this point and time.

Cash and we need to see how the trial finalizes, but we are absolutely always thinking about how we leverage the sales force when we leveraged and sales force and what that overlap of physicians might look like.

And again as we built our sales force.

<unk> and design and structure and we did that with the understanding that we would have follow on indications.

Coming and and particularly different disease areas and also different treating physicians and so we've taken great efforts to ensure that there.

Efficiency there.

And if that were to happen.

Raghuram Selvaraju: So, specifically with respect to the smoking cessation indication, are you looking at that as being primarily an indication where the principal commercialization thrust would be through advertising as opposed to boots on the ground, relative to, for example, MDD or Alzheimer's-related agitation? Or are you thinking about it in terms of a situation where you might need to set up a totally separate sales force in order to potentially market AXS05 in that indication as well? Hehehehe

So and specifically with respect to the smoking cessation indication.

Are you looking at that as being primarily and indication where the principal commercialization trust would be through advertising as opposed to boots on the ground relative.

Relative to for example, M D D or Alzheimer's associated agitation.

Or are you thinking about it in terms of a situation where you might need to feel.

Totally separate sales force in order to potentially market access all five of that indication as well.

Ariel: Yeah, Rami, it's premature for us to talk about marketing for smoking cessation. So let's first conduct the trial and see what the profile is. But, you know, those would be great questions and great problems to have, which we would certainly solve should we have positive data.

Yeah, Rami, it's premature for us to talk about.

Marketing for smoking cessation and so let's first.

And conduct the trials.

And see what the profile is and but.

Those would be.

Questions and and.

Great problems to have which will certainly solve should we have positive data.

Ariel: Okay. And then I was just wondering, I know that you haven't had the actual meeting discussion yet on the fibromyalgia candidate, but have you received any indication one way or another as to whether the FDA considers the current efficacy data package to be adequate, or if they are looking for you to conduct an entire additional registrational program aimed at adding to the efficacy data package for assembling a potentially filable, approv

Okay, and then I was just wondering I know that you haven't had the actual meeting discussion yet on the fibromyalgia candidate, but have you received any indication one way or another as to whether the FDA considers the current efficacy data package to be adequate or if they are looking for you to cut.

Duct and entire additional Registrational program aimed at adding to the efficacy data package for assembling and potentially file a bull approvable application in fibromyalgia.

Ariel: We have not met with the FDA, and we're not going to speculate on what the outcomes of those discussions might be. But we're very much looking forward to sitting down with them and discussing what we view to be unique data in this area, which is still an area of high unmet medical need. As a reminder, there are only three approved products to treat fibromyalgia, and many patients are not addressed by the small number of currently available treatments.

We have not met with the FDA and.

And and where we're not going to speculate on what the outcomes of those discussions might be.

But we're very much looking forward to sitting down with them and discussing.

What we view to be unique data.

In this area, which is still an area of high unmet medical need and as a reminder, there are only three approved products to treat fibromyalgia.

It is the condition.

It has a variety of symptoms.

Many of which.

Are not addressed by the small number of currently available treatments.

Nick Pizzie: Okay, and then lastly, just a housekeeping item on stock-based comps. How are you anticipating stock-based comp to trend this year relative to last year, and looking at your, you know, upcoming hiring plans and, in particular, your sales and marketing infrastructure build-out, should we expect a significant increase in stock-based comp expense for 2021 relative to last year? Hey Rahm, it's Nick Pizzie.

Okay, and then lastly, just a housekeeping item on.

Stock based comp.

Are you anticipating stock based comp to trend this year relative to last year and looking at your upcoming hiring plan and and.

<unk>, you know sales and marketing infrastructure build out should we expect a significant increase in stock based comp expense for 2021 relative to 2020.

Okay.

Nick Pizzie: Yeah, I can answer that question. So yeah, we did have an increase in stock-based comp year over year. And that's just correlated, obviously, to our stock price, specifically this year. And as we build a field for us, and continue to ramp up other functions. You would continue to expect an increase in stock-based comp, and it is obviously dependent on where our share price is based on the Black-Scholes calculation when we do that. And it is amortized over a four-year period, typically. So it wouldn't be all in one year when we have an impact from a field force.

Hey, Rob Hey, Rob, It's Nick Veasey, Yes, I can answer that question. So yes, we did have an increase in stock based comp year over year and.

It's just correlated obviously to our stock price.

Specifically this year and and as we build a field force.

Okay. Thanks.

And continue to ramp up other functions you would continue.

The expected increase in stock based comp and obviously dependent on where our share prices are.

Based on the Black Scholes calculation, when we do that so and.

It is <unk>.

Amortized over a four year period typically.

And for our stock based comp so it wouldn't be all in one year.

And when we when we have an impact from from our field force.

Ashwani Verma: And your next question will come from Ashwani Verma from Bank of America. Your line is open. Hi there. Thanks for taking the questions. I just had one.

Thank you.

And your next question will come from <unk> Verma from Bank of America. Your line is open.

Hi, there.

Thanks for taking the question and I just had one so and done some extra to fight that and just trying to figure it out how many of these 50 plus patents debt do you have.

Ariel: So in terms of the AXSO5 patents, just trying to figure out how many of these 50 plus patents that you have cited can be listed on the Orange Book. My understanding is that, as a new NDA, you'll have to file the form 3-5-4-2 and list the patents that pertain to the specific attributes of the drug for the MTD label in this situation. Just curious how many of the patents would meet that criterion.

It can be listed on the Orange book.

And my understanding is that as a new NDA and you'll have to file the form Stifel <unk> for due and the patents that put into this specific attributes of the debt, but the MTBE label in this and the.

And just curious how many of the guidance would meet that.

Criteria.

Ariel: Hi Ash, thanks for the question. As a reminder, we have approximately 50 or more than 50 patents in the U.S. covering XSO5, and the vast majority of those patents are Orange Book listable, and the other point to mention is that most of those patents provide protection out to 2034; the more recent ones provide protection out to 2040. And in addition, the new patents encompass different families of patents. So not only do we have pharmacokinetic patents, but we also have methods of treating disease patents. Furthermore, we would expect that the patent families would continue to expand.

Hi, Ashley and thanks, Thanks for question and as a reminder, we have.

Approximately 50 or more than 50.

Patents in the U S.

Covering exit so five and the vast majority of those patents for <unk>.

Orange book listed.

And the.

And the other.

Point to mention is that most of those patents.

Provided protection out for 2030 for the more recent ones provide protection out to 2040.

And in addition.

The.

The new patents encompass different families of patents so.

Not only do we have a pharmacokinetic patents, but we also have a method of treating disease patents for.

For the more we would.

<unk>.

And the patent families would continue to expand.

Ariel: And just to follow up, like, have you filed that formulation pattern that you talked about earlier?

Got it and just a follow up have you filed that formulation patent that you talked about earlier.

Okay.

Ariel: So I'm not certain which formulation patent you're referring to. Are you referring to a particular patent? Typically, what we do is talk about patents that have been issued. We do have some claims around our formulation specifically. So some of the new patents that have issued specifically speak to our formulation as well as a method of treating a disease. And I think what I was referring to is additional patent families, which we would expect to file in the future, so as to further expand the patent portfolio.

And so the.

Yeah.

All right.

Im not im not certain which formulation patent you're referring to are you referring to a particular patent and typically what we do is we are we.

We do.

Talk about patents that have issued we.

We do have some claims around our formulations, specifically so some of the new.

Patents that have issued specifically speak to our formulation as well as a method of treating a disease and.

And I think what I was referring to is additional patent families, which we would expect to file and in the future. So to further expand the patent portfolio.

David Timothy Hoang: Thank you so much. Thank you. Your next question will come from David Hoang from FSMBC. Your line is open. Hey, thanks for taking the questions and fitting me in here. So just a quick couple. You talked about the digital-centric approach to the, you know, the sales force and the launch. And I'm just curious as to, you know, what gives you confidence that that type of approach, you know, detailing positions in that way, would be successful versus a more traditional in-person effort by the sales force.

Thank you so much.

Okay. Thank you.

Your next question will come from David Wang from Us and.

And BC and your line is open.

Hey, Thanks for taking the questions and fitting me in here.

A quick couple.

You talked about the digital centric approach to the debt.

Sales force and the launch.

And I'm just curious as to what gives you confidence that that type of approach detailing physicians and that way it would be successful versus the more traditional in person.

Lori Englebert: Hey David, thanks for the question. Yeah, we have high confidence, mostly based on data. We do know that psychiatrists and neurologists are two of the highest adopters of remote detailing. In fact, a lot of psychiatrists we know actually prefer it. Psychiatrists actually trend anywhere from 60 to 70% of their details are remote, and that's recent data, and that is actually higher than data even six months ago when the pandemic was much more prevalent.

By the sales force.

Hey, guys. Thanks for the thanks for the question yes.

Yes, we have high confidence mostly based on data, we do know that psychiatrist and neurologist are two of the highest for doctors for.

From a detailing and fact a lot of psychiatrist we know actually prefer it.

Psychiatrists actually trend anywhere.

From 60% to 70% of their details are remote and Thats a recent data.

And that is actually higher than data even.

Six months ago, when the pandemic was actually.

Lori Englebert: So we feel pretty confident that this is a sound approach, and we certainly are not alone in this. Most companies are doing this, and physicians are currently dictating how they want to see sales reps. So they will tell you if they want you to come in person or if they want you to come in via remote detail, and we're going to use data and analytics to make sure that we're approaching them correctly.

And much more prevalent so so.

And we feel pretty confident that this is this is a sound approach and we certainly are not alone and this most companies are doing.

Joining us and physicians right now are currently dictating how they want to see our sales reps. So they will tell you. They want you to come in and person or they want you to come in.

And ever more detail and.

We were going to use data and analytics to make sure that we're approaching them correctly.

Ariel: Okay, great. That's really helpful. Thanks. And then just on O5 in Alzheimer's agitation. Just wondering about the environment for usage there. Do you imagine that the drug would be mostly something for the home and the community setting, or would you also expect to see sort of a large uptake in the long-term care setting?

Okay, Great. That's really helpful. Thanks, and then just saw and O five.

In Alzheimer's agitation just wondering about the.

Environment for usage, there do you.

And that the drug would be mostly something for the home and the community setting.

And would you also.

To see sort of a large uptake and the long term care setting.

Ariel: So our studies were, well, we conducted one trial, so our pivotal trial, and also just our currently ongoing study, were conducted in patients who were based in the community. And we did that for a lot of reasons.

So.

So our studies.

Work.

Well, we conducted one trials so our pivotal trial and also just our currently ongoing study.

And is or were conducted in patients who are based and the community and.

And we did that for.

Or.

A lot of reasons and.

David Timothy Hoang: But there is... There's no reason to believe that the drug would not work in any setting, and the reason why we focused on community-dwelling patients is that one, you want to prevent patients from actually being institutionalized. So if you can't treat them, you want to keep them out of the hospital and out of nursing homes. However, once you show that the product works, there's no reason to think that the pharmacology is going to change, depending on the setting.

And then.

But there is.

And Theres no reason to believe that the drug would not work in any study and the reason why we focused on community dwelling patients is one.

You want to prevent patients from actually being institutionalize. So what if you can treat them you wanted to keep them out of the hospital and out of nursing homes.

And and so.

And so.

And however.

And once you show that the product works and we.

No reason to think that.

The pharmacology is going to change depending on the setting.

Operator: Got it. Great. Thanks so much for taking my call. We have no further questions. Thank you. I turn the call back over to the presenters for closing remarks.

Got it great. Thanks, so much for taking my questions.

Okay great.

We have no further questions. Thank you I turn the call back over to the presenters for closing remarks.

Ariel: Well, thank you all for joining us on the call today. This year will be an important one for Axsome, as we move closer to potential commercialization of our product candidates. We look forward to keeping you updated on our progress.

Well, thank you all for and for joining us on the call today. This year will be an important and one for axon.

As we move closer to potential commercialization and our product candidates. We look forward to keeping you updated on our progress.

Operator: Thank you, everyone. This will conclude today's conference call. You can now disconnect.

Yeah.

Thank you everyone and this will conclude today's conference call you can now disconnect.

Okay.

Okay.

Yes.

And.

And.

And.