Q2 2021 Axsome Therapeutics Inc Earnings Call

Operator: Good morning, and welcome to the Axon Therapeutics conference call.

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

Operator: 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, Mr.

On a fee all participants are in a listen only mode.

There will be a question and answer session and instructions will follow at that time I'm.

And as a reminder, today's conference call is being recorded.

I would now like to turn the conference over to your host Mr. Mark Jacobson Chief.

Operator: Mr. Mark Jacobson, Chief Operating Officer at Axon Therapy 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 second quarter of 2021 crossed-the-wire a short time ago and is available on our website at axon.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 investments.

And operating officer and Axon 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 on the company's financial results for the second quarter of 2021 and crossed the wire a short time ago and is available on our website at axon and Dot com.

During today's call, we will be making certain forward looking statements. These.

These statements May include statements regarding among other things.

And I can see safety and intended to utilization and our investigational agents.

Clinical and non clinical plans, our plans to present or report additional data anticipated conduct and the source and future clinical trials regulatory plans and future research and development plans and.

Commercial plans and possible intended use of cash and investments.

Operator: These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainty that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports.

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 and the forward looking statements.

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

Mark L. Jacobson: We are cautioned not to place due reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today are Dr. Aereotabuto, Chief Executive Officer; Nick Peasy, Chief Financial Officer; Dr. Kevin La Liberty, Executive Vice President, Product Strategy; Lori Engelbert, Senior Vice President of Commercial and Business Development; and Dr. Amanda Jones, Senior Vice President of Clinical Development.

You're cautioned not to place undue reliance on these forward looking statements, which are only made as of today's date and the <unk>.

<unk> disclaims any obligation to update such statements.

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

Mark L. Jacobson: Aero will first provide an overview of the company and then review recent developments and upcoming milestones. Following Aero, Lori will provide a commercial update, and then Nick will review our financial results. We will then open the line for questions. Questions will be taken in the order they are received. And with that, I will turn the call over to Ariel.

<unk> will first provide an overview on the company and then review recent developments and upcoming milestones salary area Laurie will provide a commercial update and then Nick will review our financial results.

And then open the line for questions questions will be taken in the order they are received and with that.

I will turn the call over to Ariel.

Aereotabuto: Thank you, Mark. Good morning, everyone, and thank you all for joining Axome Therapeutics' second quarter 2021 financial results and business update conference call. Since our last update, we continue to make significant strides toward becoming a premier CNS biopharmaceutical company focused on delivering potentially life-changing medicines to people living with serious CNS conditions. I will provide an update on our development pipeline before turning it to Lori, who will provide a commercial update. Starting with our first lead product candidate, XS05, which is undergoing an NDA review for the treatment of major depressive disorder with a Bedoufa date of August 22, 2021.

Thank you Mark good morning, everyone and thank you all for joining axon therapeutics second quarter, 'twenty, 'twenty, 1 and financial results and business update conference call.

Since our last update we continue to make significant strides towards becoming a premier CNS biopharmaceutical company focused on delivering potentially life changing medicines to people living with serious CNS conditions.

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

Starting with our first lead product candidate, except so 5 which is undergoing and India review for the treatment of major depressive disorder with a <unk> date of August 22021.

Aereotabuto: On July 30th, we received a letter from the FDA stating that as part of their ongoing review of our NDA, they have identified deficiencies that preclude discussion of labeling at this time. The letter did not state what the deficiencies were. However, immediately upon receipt of the letter and continuing through today, we have been in communication with the FDA to attempt to learn the nature of these deficiencies so that we can address them.

On July 30th we received the letter from the FDA, stating that as part of their ongoing review of our NDA. They have identified deficiencies that preclude discussion labeling at this time.

The letter did not state what the deficiencies are.

Immediately upon receipt of the letter and continuing through today, we have been and communication with the F. D. A to attempt to learn the nature of these deficiencies. So that we can address them.

Aereotabuto: In response, the FDA has informed the company that its review is ongoing and that they have no specific questions for the company at this time. Although the letter stated that the notification does not reflect a final decision on the information under review, this development may lead to a delay in the potential approval of AXSO5. We will keep you informed as we learn more.

And response you have T has informed the company that their review is ongoing and that they have no specific questions for the company at this time.

Although the letter stated that the notification does not reflect a final decision on the information under review this development may lead to a day late and the potential approval of <unk>.

So 5.

We will keep you informed as we learn more.

Aereotabuto: This morning, in a separate announcement, we announced positive typeline results for the Phase 2 merit trial of AXO5 in treatment-resistant depression. XS05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of depressive symptoms as compared to placebo with a p-value of 0.002. AXO5 also met a key secondary endpoint by significantly preventing relapse of depression over at least six months, with relapse occurring in 36% of subjects receiving placebo compared to zero subjects receiving AXO5, a P value of 0.004. The robust results from this small trial add to the body of controlled data demonstrating the benefits of AXO5 in depression. XSO5 is also being developed for the treatment of Alzheimer's disease agitation.

This morning, and a separate release, we and.

Mounts positive top line results for the Phase II Merit trial of access so 5 and treatment resistant depression.

Yeah. So 5 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of depressive symptoms as compared to placebo with a P value of 0.00 too.

Yeah. So 5 also met the key secondary endpoint like significantly preventing relapse of depression over at least 6 months with relapsed occurring and 36% of subjects, receiving placebo compared to zero subjects, receiving excess so 5 with a P value of 0.004.

The robust results from this small trial and to the body of controlled data demonstrating the benefits of excess so 5 and depression.

The successful 5 is also being developed for the treatment of old timers disease agitation.

Aereotabuto: Enrollment in the Phase 3, a core trial for the syndication, is progressing, with study completion anticipated in the fourth quarter of 2022. Moving on to our second lead product candidate, XS-O-7, a multi-mechanistic acute treatment for migraine. The NDA for AXSO7 was filed at the end of the second quarter, and we expect to announce the FDA's decision regarding its acceptance of the filing this quarter. With 2 NDE filings, Axome is approaching the commercialization stage for these programs.

Enrollment in the phase 3 of core trial and for the syndication is progressing with study completion anticipated in the fourth quarter of 2020.2.

Moving on to our second lead product candidate, except so 7 day.

Multi mechanistic acute treatment for migraine.

And the NDA for access so 7 was filed at the end of the second quarter and we expect to announce the Fda's decision regarding its acceptance of the filing this quarter.

With 2 when do your filings axon is approaching commercialization stage for these programs.

Aereotabuto: Lori will provide some details on our pre-launch commercial activities to ensure successful launches, assuming FDA approval. Meanwhile, the rest of our differentiated late-stage pipeline continues to advance. Our AXS12 product candidate for Narcolepsy is on track for initiation of the planned phase three trial this quarter, and we anticipate submitting an NDA for our AXS14 product candidate for the management of fibromyalgia in the fourth quarter of 2022. I will now turn the call over to Lori, who will provide a commercial update. Thank you, Ario, and good morning, everyone.

Lori will provide some details on our prelaunch commercial activities to ensure successful launches assuming FDA approval.

The rest of our differentiated late stage pipeline continues to advance.

Our excess 12 product candidate for narcolepsy is on track for initiation of the planned phase III trial this quarter and.

And we anticipate submitting an NDA for our excess 14 product candidate for the management of fibromyalgia till the fourth quarter of 2020.2.

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

Thank you Ariel and good morning, everyone.

Lori Englebert: This is an exciting time at Axum as we continue to prepare to launch both AXSO5 for major depressive disorder and AXSO7 for the acute treatment of migraine. Today, I will give you an update on our commercial activities as it relates to launch readiness. The U.S., and the need for awareness and support for those suffering is apparent. Recently, we have witnessed an increased spotlight on mental health as celebrities and athletes are bringing awareness to the forefront for the many Americans who may be suffering.

This is an exciting time and Exxon and we continue to prepare to launch both access and 5 and major depressive disorder, and access and I start and when the acute treatment of migraine.

Today I won't give you an update on our commercial activities as it relates to not ready now.

The U S is in the middle of a mental health crisis.

And the need for awareness and support for that and suffering as a parent free.

Recently, we have witnessed and increased spotlight on mental health and celebrities and athletes and bringing awareness to the forefront and many Americans who may be suffering.

Lori Englebert: During the pandemic, prevalence of depression symptoms in U.S. adults increased greater than fourfold versus 2019, and one out of every three U.S. adults experienced depressive symptoms in 2020. Given the personal and economic burden associated with mental health conditions, there is an undeniable urgent need to bring support to those affected.

During the pandemic prevalence of depression symptoms and U S. Adult has increased greater than 4 fall versus 2019.

1 out of every 3 U S adult experience depressive symptoms and 2020.

Given the personal and economic burden associated with mental health conditions.

And undeniable urgent need to bring support to those affected.

Lori Englebert: If approved, AXS05 would be an important new treatment option for the many Americans living with depression. We are prepared and ready to bring this meaningful innovation to patients by commercializing the product soon after potential approval. If approval is received on our expected PDUFA date of August 22nd, we anticipate launch within three months. Our commercial launch strategy is innovative and purposeful with the intent to bring meaningful new products to patients in an efficient and effective way.

If approved and access to 5 would be and important new treatment option for the many Americans living with depression.

We are prepared and ready to bring this meaningful innovation to patients.

By commercializing the product soon after potential approval.

And if approval is received on our expected put it on the date of August 22nd we anticipate launch to occur within 3 months.

Our commercial launch strategy and innovative and purposeful with the intent to bring meaningful new products to patient and an efficient and effective way.

Our digital centric commercialization part D. C. C platform is now fully implemented and testing and the platform for execution at launch is well underway.

As a reminder, we have designed our D. C C platform to use streamline systems and digital enablement tool combined with sophisticated data and analytics to allow for more effective and efficient and meaningful engagement with physicians and consumers.

Lori Englebert: Our Digital Centric Commercialization or DCC platform is now fully implemented, and testing of the platform for execution at launch is well underway. As a reminder, we have designed our DCC platform to use streamlined systems and digital enablement tools combined with sophisticated data and analytics to allow for a more effective, efficient, and meaningful engagement with physicians and consumers. Importantly, our field leadership team is now fully staffed. I am incredibly impressed by the caliber, experience, and talent that we have attracted and look forward to their leadership.

And importantly, our field leadership team is now fully staffed.

And incredibly impressed by the caliber experience and talent and we have attracted and look forward to NAV leadership.

Sales representative hiring has commenced with all offers being made contingent upon approval.

We anticipate having all sales representatives onboard and trained I launch.

And market access team continues to engage with payers and ongoing permitted discussions and.

Chairing awareness and axon and our pipeline and the clinical profile of access of 5.

We look forward to engaging with payers immediately after approval.

Our market access team is also actively setting up a comprehensive patient support services to ensure that patients can easily receive product and prescribed.

Lori Englebert: Field representative hiring has commenced, with all offers being made contingent upon approval. We anticipate having all field representatives on board and trained by launch. The Market Access Team continues to engage with payers in ongoing, permitted discussions, ensuring awareness of AXSF5, our pipeline, and the clinical profile of AXSF5. We look forward to engaging with payers immediately after approval. Our market access team is also actively setting up comprehensive patient support services to ensure that patients can easily receive the product if prescribed. It is important to note that although our launch readiness discussions are currently focused on AXSO5, we are also actively preparing for a potential, subsequent

And it is important to note that although our and launch readiness discussions are currently focused on the expense side..5 we are also actively preparing for a potential subsequent much of excess oven and the acute treatment of migraine.

And to build heading disease that continues to have a tremendous unmet need and impacts and estimated 37 million U S. Adults.

The differentiated clinical profiles for both access and oxide and access are 7 has the potential to bring significant benefit to patients and the physicians who treat them.

We are excited about the opportunity to bring these meaningful products to market.

I will now turn it over to Nick and I will review our financials.

Thank you Lori and good morning, everyone.

And I will discuss our second quarter 2021 results and provide some financial guidance.

We ended the second quarter with approximately 141 million and cash compared to roughly $165 million and cash at the end of the first quarter, a net decrease of approximately $23.5 million.

Lori Englebert: potential subsequent launch of AXS7 for the acute treatment of migraine, a debilitating disease that continues to have a tremendous unmet need and impacts an estimated 37 million U.S. adults

R&D expenses were $14.5 million for the quarter ending June 32021 versus $10.5 million for the comparable period in 2020.

Nick Pizzie: The differentiated clinical profiles for both AXO5 and AXSO7 have the potential to bring significant benefits to patients and the physicians who treat them. We are excited about the opportunity to bring these meaningful products to market. I will now turn it over to Nick, who will review our financial results. Thank you, Lori, and good morning, everyone. Today, I will discuss our second quarter 2021 results and provide some financial guidance. We ended the second quarter with approximately $141 million in cash compared to roughly $165 million in cash at the end of the first quarter, a net decrease of approximately $23.5 million.

The increase was driven by cost to support the NDA filings and and personnel expense, which includes an increase and head count along with an increase and noncash stock compensation expense.

During the second quarter, we received a refund from the FDA and the amount of $2.9 million, which was paid and the first quarter related to the producer application fee for access so 5 and N V D. As part of the FDA granting us a small business waiver.

The current quarter included a $2.9 billion dollar charge related to the produced the application fee for the NDA submission for <unk>, 7 and the acute treatment of migraine.

Nick Pizzie: R&D expenses were $14.5 million for the quarter ending June 30th, 2021, versus $10.5 million for the comparable period in 2020. The increase was driven by costs to support the NDA filings and in personnel expense, which includes an increase in headcount, along with an increase in non-cash stock compensation. During the second quarter, we received a refund from the FDA in the amount of $2.9 million, which was paid in the first quarter related to the Padufa application fee for AXS-O-5 and MDD as part of the FDA granting us a small business waiver.

G&A expenses were $16.3 million for the quarter, ending June 32021, and $7.2 million for the comparable period in 2020. The increase was primarily due to pre commercial activities and personnel expense, which includes an increase and head count along with an increase in non cash stock compensation expense.

Net loss was $32.3 million or <unk> 86 per share for the quarter ended June 32021, compared to a net loss of $18.3 million or <unk> 49 per share for the comparable period in 2020.

As a reminder, we currently have $225 million term loan facility of which $175 million and funding remains available. This committed non dilutive capital gives us additional financial flexibility through both anticipated potential commercial launches for access so 5 and access those.

Nick Pizzie: The current quarter included a $2.9 million charge related to the Padufa application fee for the NDA submission for AXSO7 in the acute treatment of migraine. G&A expenses were $16.3 million for the quarter ending June 30, 2021, and $7.2 million for the comparable period in 2020. The increase was primarily due to pre-commercial activities and personnel expense, which includes an increase in headcount, along with an increase in non-cash stock compensation expense.

On.

We believe our current cash position of $141 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 2020.4.

That concludes our second quarter 2021 financial review I will now turn the call back to Mark to lead the Q&A discussion.

Nick Pizzie: The net loss was $32.3 million or 86 cents per share for the quarter ending June 30th, 2021, compared to a net loss of 18.3 million or 49 cents per share for the comparable period in 2020. As a reminder, we currently have a $225 million term loan facility, of which $175 million in funding remains available. This committed, non-diluted capital gives us additional financial flexibility through both anticipated potential commercial launches for AXS05 and AXS7.

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

Okay.

Certainly sir at this time I would like to take any questions you might have for SCD. If he would like to ask a question. Please press star 1 on your telephone keypad.

Our first question comes from Charles Duncan from Cantor Fitzgerald.

Okay. Good morning folks area and team. Thanks for taking my question and congratulations on the Merit trial results.

However, the first question that I have is regarding access so 5 and M. D. D. I know youre not going to be able to be all that definitive but I'm I'm wondering if you can speculate at all as to the nature of the questions that are being contemplated by by the agency.

Nick Pizzie: We believe our current cash position of $141 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.

Was there for you know by and in terms of the trial designs that supported this N D. A.

Mark L. Jacobson: That concludes our second quarter 2021 financial review. I will now turn the call back to Mark to lead the Q&A discussion. Thank you, operator. May we please have our first questions? Certainly, sir. At this time, I would like to take any questions on my tab for us today. If you would like to ask a question, please press star 1 on your telephone keypad.

Yeah.

Good morning, Charles and thank you for for the questions.

So with regards to the deficiencies, we just want to reiterate that we do not know what the deficiencies are and so the letter did not state what the deficiencies are or even what discipline and they've retained too.

As a reminder, we did received priority review for this application and this was the very large submission and and package to what extent that has oh.

And impact on the current situation and so it's hard to say, but up until now the review has been going on track from our perspective, and we believe that we've responded adequately to them for questions. During the review period and importantly, we have not been made aware of any deficiencies and the application up to this point.

Operator: Our first question comes from Charles Duncan from Cantor Fitzgerald.

Charles Cliff Duncan: Hey, good morning, folks, Aereo and team, thanks for taking the question, and congratulations on the merit trial results. However, the first question that I have is regarding AXO5 and MDD.

So since we've learned of.

And existence of these deficiencies through the letter we have made attempts to.

Aereotabuto: I know you're not going to be able to be all that definitive, but I'm wondering if you can speculate at all as to the nature of the questions that are being contemplated by the agency. Was their full, you know, buy-in in terms of the trial designs that supported this NDA? Good morning, Charles, and thank you for the questions.

Learn what the deficiencies are and up to this point, we still don't know and as soon as we find out and we'll let you know.

Okay, and then with regard to the manufacturing inspections that occurred during the review.

Or are there any observations debt that were noted for 83 observations.

Aereotabuto: So with regard to the deficiencies, we just want to reiterate that we do not know what the deficiencies are. The letter did not state what the deficiencies are or even what discipline they pertain to. As a reminder, we did receive priority review for this application. This was a very large submission and package. To what extent that has an impact on the current situation, it's hard to say.

Yeah.

Okay.

So.

Charles We we Havent commented on on the specifics of them.

And the inspection.

And so.

To this day, we have not been aware of any 40 three's in connection with any of our inspection.

Okay. Okay, and then if I could ask 1 question on the Merit trial very intrigued with T. R. D results as you know there's a line of work being done by psychedelic oriented companies.

Aereotabuto: But until now, the review has been going on track from our perspective. We believe that we've responded adequately to all of the questions during the review period. And importantly, we have not been made aware of any deficiencies in the application up to this point. So since we've learned of the existence of these deficiencies through the letter, we have made attempts to learn what the deficiencies are. But up to this point, we still don't know. And as soon as we find out, we will let you know. Okay, and then with regard to the manufacturing inspections that occurred during the review, were there any observations that were noted (483 observations?

To generate you know efficacy and TRT and I and I guess I'm wondering as you think about.

And the unmet need there.

Each of the 2 endpoints here and most important to the time to relapse.

For the you know call it responder rate over 6.6 months they are 36% control.

Having response or having a relapse versus zero percent and the drug on line when you talked to Kols, what do they focus on.

Aereotabuto: So, Charles

Aereotabuto: Charles, we haven't commented on the specifics of the inspections. And so, um, to this day, we have not been aware of any 483s in connection with any of our institutions.

Yeah.

And so what Vince Thanks for that question Charles on on Merit. So we are the wave and our study was designed and we looked at the time to relapses are the primary endpoint. This is the standard.

Charles Cliff Duncan: Okay, and then I could ask one question on the merit trial. I'm very intrigued with the TRD results. As you know, there's a lot of work being done by psychedelic-oriented companies to generate, you know, efficacy and TRD. And I guess I'm wondering, as you think about the unmet need there, which of the two endpoints is most important for time to relapse or the, you know, call it responder rate over six months, the 36% control, having a response or having relapse versus 0% in the drug arm. When you talk to KOLs, what do they focus on? So thanks for that question, Charles on merit.

And for Relapse prevention trial, and but we also looked at just prevention of relapse as a key secondary endpoint and.

And that is a very important and point to look at so it's 1 thing for a drug to actually delay relapse of depressive symptoms, but its a higher bar to actually prevent relapses period, and and so I think that both endpoints would be relevant to clinicians.

But certainly preventing relapses and if that is possible is very relevant and and very and something that clinicians would look for and as the results show.

In the and the mirror trial.

Or at least 6 months of treatment and and that's the minimum and some of these patients that were treated out to a year.

Aereotabuto: So in the way that our study was designed, we looked at time to relapse as the primary endpoint. This is a standard endpoint for relapse prevention trials. And we also looked at time, just prevention of relapse, as a key secondary endpoint, and that is a very important endpoint to look at. So it's one thing for a drug to actually delay relapse of depressive symptoms, but it's a higher bar to actually prevent relapse.

No relapses word.

Okay.

Very good last question for Lori sales contingent offers can you share with us and number of them that you have out.

And importantly, the timelines how how long to those offers last day.

And I assume they're contingent on approval is I think you mentioned.

Aereotabuto: And so I think that both endpoints would be relevant to clinicians, but certainly preventing relapse, if that is possible, is very relevant and is certainly something that clinicians would look for. And as the results show, in the Merit trial, over at least six months of treatment, and that's the minimum. Some of these patients were treated out to a year, no relapses occurred. Okay. Very good. Last question for Lori

Yeah, Hey, Charles and and that's right. They are they are being made contingent upon approval.

And you know, we're still not revealing the size of the sales force.

And I want to and give you.

That estimate just yet and we are.

Well on our way of ensuring that we will have everyone on board by launch if we stay on the current timeline.

Okay. Thanks for taking the questions.

Yeah.

Thank you. Our next question comes from Marc Goodman with SVP Leerink. Your line is open.

Lori Englebert: Sales contingent offers Can you share with us the number of them that you have out, and importantly, the timelines; how long do those offers last? You know, and I assume they're contingent on approval, as I think you mentioned. Yeah, hey, Charles, and that's right, they are being made contingent upon approval, and, you know, we're still not revealing the size of the sales force, so I don't want to give you that estimate just yet. We are well on our way to ensuring that we will have everyone on board by launch if we stay on. Okay, thanks for taking the question.

Yes, good morning, Eric.

And you can kind of help us understand how you're thinking about what the FDA is asking for you. So maybe take us back to your your meetings with FDA on your pre NDA meeting pre filing your share.

And anything that's gone along and the process.

What did the FDA say was needed here and.

And in the filing and just talk about whether you feel like you've checked those boxes and then you can give us a little bit more detail I mean.

And the previous question you talked a little bit about CMC. So is it your understanding that you know CMC is completely done like everything was stability everything like you know.

Operator: Thank you. Our next question comes from Mark Goodman with SVB, the ring. Your line is open.

There were no issues there I mean, we're just trying to understand here and what happened obviously before it too.

Mark Goodman: Yes, good morning. Hario, can you kind of help us understand how you think about what the FDA is asking of you? So maybe you can take us back to your meetings with FDA, your pre-NDA meeting, your pre-NDA meeting, pre-filing, you know, anything that's gone along in the process. What did the FDA say was needed in the filing, and just talk about whether you feel like you've checked those boxes, and then you can give us a little bit more detail.

And and and we're just not going to find out until you have a meeting with them and that you requested.

You requested a meeting I assume.

Or did you I guess you have to wait until that's due for day.

Maybe you could give us a little more color there. Thanks.

Okay.

Well, thanks, Mark for the question.

And so.

I just want to reiterate that we have not been made aware of what the deficiencies are.

With regards to the process up to this point.

Mark Goodman: I mean, in the previous question, you talked a little bit about CMC, so is it your understanding that, you know, CMC is completely done? Like everything was stable, everything like, you know, there were no issues there? I mean, we're just trying to understand here what happened. Obviously, you are, too.

And the process has been going very smoothly and as a reminder, this is a breakthrough therapy designation product. So we felt that we've gotten very close.

And back from the agency.

You know every step along the way, including our pre NDA meeting and as a reminder, the filing was accepted and non linguistic was it accepted but it was granted priority review so that would be an indication that all of the boxes have been checked.

Aereotabuto: And are we just not going to find out until you have a meeting with them? And you've requested a meeting, I assume, or I guess you have to wait until the PDFA date. Maybe you can give us a little more color there. Thanks.

With regards to our CMC.

On the CMC work was complete and probably the agreements prior to filing the application and.

And during the review and we've answered questions on adequately and we feel of that process has been going smoothly.

Aereotabuto: Well, thanks Mark for the question. So I just want to reiterate that we have not been made aware of what the deficiencies are. With regard to the process up to this point, the process has been going very smoothly. As a reminder, this is a breakthrough therapy designated product, so we feel that we've gotten very close feedback from the agency every step along the way, including our pre-NDA meeting. And as a reminder, the filing was accepted, and not only was it accepted, but it was granted priority review. So that would be an indication that all the boxes have been checked with regard to CMC. All of the CMC work was completed for the agreements prior to filing the application.

And in terms of.

And meeting with the agency as you can imagine upon receiving the letter we've made attempts to learn what the nature of the deficiencies are moving.

Requesting a meeting.

Now there is still time on the Purdue for clock admittedly, it's a it's the time is dwindling.

However, as soon as we learn of what the deficiencies or Av or any additional details.

And you'll be the first day.

Okay.

Just talk about the manufacturing plants have they been inspected completely like everything as far as you're concerned that belt box is checked I mean, this is probably not a manufacturing issue.

So mark can provide you some more details on that but as a reminder, the <unk>.

<unk>.

And is being manufactured.

Aereotabuto: And during the review, we've answered all questions adequately, and we feel that that process has been going smoothly. And in terms of requesting a meeting with the agency, as you can imagine, upon receiving the letter, we've made attempts to learn what the nature of the deficiencies are, including requesting a meeting. Now, there's still time on the Purdue clock, you know, admittedly, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's, it's,

And our commercial.

Blue Chip CMO that regularly gets gets inspected.

Hmm.

Yeah and <unk>.

Good morning, So just a reminder, on the drug substances are are the drug substances are available.

And we'll under open DNS here and the U S and from sources that.

We are comfortable with that and that we have ourselves audited and and.

And and and inspected so so.

That's the drug substance in terms of drug product as Eric mentioned.

Aereotabuto: Um, however, you know, as soon as we learn of, of, of, of, of, of, of any additional details, you will be the first. Did just talk about the manufacturing plants? Have they been inspected completely? Like everything, as far as you're concerned, that box is checked?

That is a oh.

Major C D M O that that makes multiple commercial products and has numerous facilities.

And the facility that we use and North America and.

And.

We have also done on our inspections prior to engagement and are there you mentioned that that facility is regularly inspected by FDA and we are not.

Aereotabuto: I mean, this is probably not a manufacturing issue. So Mark can provide you with some more details on that, but as a reminder, the product is being manufactured at a commercial blue-chip CMO that regularly gets inspected. Yeah, hey, Mark, in the morning. Just a reminder, so the drug substances are, the drug substances are available under OpenDMS here in the U.S. from sources that we are comfortable with that we have ourselves audited and inspected.

And as mentioned earlier with any of our inspections were not aware of any.

Or have not been made aware of any.

Issues that may preclude or may lead to a development like this.

I mean I know this might just be a basic question because you were.

Accepted but you have the appropriate.

Numbers of patients for safety and you've got 2 positive studies with the FDA basically said you unequivocally you've had 2 studies like I'm, just trying to understand where the problem is.

Aereotabuto: That's the drug substance in terms of drug product, as Ariel mentioned, that is a major CDMO that makes multiple commercial products, numerous facilities, and the facility that we use is in North America. We have also done our inspections prior to engagement, and as Ariel mentioned, that facility is regularly inspected by FDA, and we are not, as mentioned, as mentioned, as mentioned earlier, with any of our inspections, we're not aware of, or have not been made aware of any issues that may preclude or may lead to a development, I mean, I know this might just be a basic question because you were accepted, but you have the appropriate numbers of patients for safety.

Okay.

We are too and as soon as we are.

Or made aware of exactly what the deficiencies are and we will communicate them to you.

Yeah.

Alright. Thanks.

Thank you.

Our next question net from the meal day Vaughan with Mizuho. Your line is open.

Great. Thanks for taking my question, maybe 1 more just on this deficiencies.

Later, we have seen a few of these now and.

The last few months from and from other companies as well. So just trying to get a sense I think we and when we started a few weeks a few months ago with Acadia to some thought and maybe because of COVID-19 and the FDA being strapped and.

And the project managers kind of coming in and out of the review process that that may have played a role.

Aereotabuto: You've got two positive studies that the FDA basically said to you unequivocally: you have two studies. Like, I'm just trying to understand where the problem is. We are, too, and as soon as we are made aware of exactly what the deficiencies are, we will communicate.

And that was also sort of speculation, but just I'm curious if there's anything during your route.

And your review process, and where maybe there were you.

And no changes to personnel or different project managers, along the way and maybe I'll, let maybe that's led now just sort of deficiency notice very late in the process.

Mark Goodman: Thank you. Our next question is from Bamil, with Mizoo. Your line is open.

Bamil: Great, thanks for taking my question. Maybe one more on this deficiencies letter. We've seen a few of these now in the last few months from other companies as well. So just trying to get a sense, I think, you know, when we saw it a few months ago with Acadia, there was some thought that maybe because of COVID and the FDA being strapped and, you know, project managers kind of coming in and out of the review process, that that may have played a role.

And then my second question just on.

Separately with the TRT data just curious again I think as you've described it before is ultimately youre not expecting anything around TRT in the label or an indication and is even more of a sort of medical education purposes. Can you just remind me if I'm thinking of that correctly or or do you think that ultimately you will be able to try and get a TRT and.

Acacia as well thanks.

So what.

Bamil: Again, I think that was also sort of speculation, but just curious if there's anything during your view, during your review process where maybe there were, you know, changes to personnel or different project managers along the way, and maybe that led, maybe that's led now to this sort of deficiency notice very late in the process.

Take those 2 questions in reverse order with regards to the Merit study and and TRT. Our current focus is ensuring approval and launch of it because it'll 5 and and D. D. So we are very excited by the results of the Merit trial. This is an additional source of data and obviously, we'll be thinking about.

And what those results and need for any kind of future plans, but currently our focus is to ensure approval and module makers 5 and M. D D with.

Aereotabuto: And then my second question, just separately with the TRD data, just curious, again, as you've described it before, is ultimately you're not expecting anything around TRD in the label or an indication, and there's more for sort of medical education purposes. Can you just remind me of that if I'm doing that? Can you think of that correctly, or do you think that, ultimately, you will be able to try and get a TRD indication as well? So we'll take those two questions.

With regards to changes.

The FDA during the review process.

We do.

Recognize as you do also that the.

And the agency has been.

Definitely stressed resource wise.

As a result of the Covid pandemic.

With.

As it relates to our particular application and Theres nothing that we can point to specifically.

Aereotabuto: So we'll take those two questions in reverse order. With regard to the Merit Study and TRD, our current focus is ensuring approval and launch of XSO5 in MDD. So we are very excited by the results of the Merit trial. This is an additional source of data. And, you know, obviously, we'll be thinking about what those results mean for any kind of future plans. But currently, our focus is to ensure approval for the launch of AXO5.

But what we do know that globally overall with the FDA.

Is like every other organization.

Dealing with them with the.

The COVID-19 pandemic and reach.

And the resource screen that come from that.

Okay. Thank you.

Yes.

Thank you.

The next question is from Vikram, and Peru head with Morgan Stanley. Your line is open.

Great. Good morning, Thanks for taking.

Our questions.

Aereotabuto: 5 in MDD. With regard to changes at the FDA during the review process, you know, we do recognize, as you do, also that the agency has definitely been stressed resource-wise as a result of the COVID pandemic. As it relates to our particular application, there's nothing that we can point to specifically. But we do know that globally, overall, the FDA is like every other organization dealing with the COVID pandemic and the resource strain that comes from that.

Just 2 from my side.

So just to clarify.

Assuming things progress with the.

And the excess of 5 and D E and.

Some clarity does become available and the near term what.

And what exactly is the plan for and.

Corporate and data from the Merit study.

Towards your commercial efforts and if there is 1 and.

And secondly, just going back to the.

Deficiency letter I think the press release mentioned.

Vikran: Our next question is from Vikran, with Morgan Standing. Your line is open.

And some language around post marketing commitment was there any additional color available on on that topic.

Vikran: Great, good morning. Thanks for taking our questions. Just two from my side.

Vikran: So just to clarify, assuming things progress with the excess of FI's NDA and some clarity does become available in the near term, what exactly is the plan for incorporating data from the merit study towards your commercial efforts, if there is one?

From the FDA about.

Yeah.

Specific.

On the India.

Yeah.

So what so with regards to the debt.

The part of the language that we put it in the press release around post marketing commitments.

Aereotabuto: And secondly, just going back to the deficiency letter, I think the press release mentioned some language around post-marketing commitment. Was there any additional color available on that topic from the FDA about that specific area of the NDA? So with regard to the part of the language that we put in the press release around post-mortaging commitments. That's identical language from the letter, so we wanted to just provide it to you as we got it.

Identical language from from the letters and we wanted to just provided to you as as we got it.

So there are no specifics so nothing was identified there either.

With regards to specifics on them.

And so we provided you exactly.

It's been provided to us.

And then with regards to to Merit.

We should mention that that we have made the agency aware as you can imagine the results on.

Aereotabuto: So there are no specifics, so nothing was identified there either with regard to specifics, or and so we've provided you with exactly what was provided to us. And then, you know, with regard to Merritt, we should mention that we have made the agency aware, as you can imagine, of the results. The study was unblinded over the weekend, and so it is clearly relevant to depression as an indication in general, so MDD. And our focus is, of course, the indication that we have filed for, which is MDD and not TRD. And I'll turn it over to Lori to discuss how the study might impact commercialization.

The study was on blinded over the weekend and.

It is clearly relevant to depression as a as an indication in general So M D D.

And we.

Our focus is of course, the indication and the final 4 which is M E T and non TRT and.

And and I'll turn it over to Laurie to discuss how how the study might impact commercialization.

Yeah, you know the data and given that it was a phase 2 will just be used as supplemental data and our conversations.

The data.

And are very very relevant.

Relevant to patients that physicians are having a difficult time training them and and that only provides further.

Further validation to the body of work that access and 5 as I.

Lori Englebert: Yeah, you know, the data, given that it was phase two, will just be used as supplemental data in our

And I do believe that the durability and is expressed in this patient population from the study will be highly relevant to physicians as well.

Lori Englebert: use the supplemental data in our conversations, the data, very, very relevant to patients that physicians are having difficulty with, and that only provide further validation for the body of work that AXSI. I do believe that the durability that is expressed in this patient population from the study will be highly relevant. Got it. And then there was a quick follow-up. So understanding that this is relatively new news for you as well, but do you have any current thoughts on how the deficiency letter impacts your plans for XSO5 outside of MDD, whether that's with the ADA program or a meeting that you were supposed to have on smoking excitation with the FDA later this quarter? We don't believe that it has any impact on the other, in this case. Okay, I understand. Thank you.

Got it and then a quick follow up.

So understanding that this is relatively.

New news for you as well, but.

And you have any current thoughts on how the deficiency letter impacts your plans for excess and 5 outside of and duty whether that's with.

The ATM program or a meeting day, you were supposed to have on smoking cessation and with the FDA and later this quarter.

Yeah.

We don't believe that it has any impact on the other indications.

Okay understood. Thank you.

Thank you our next question and this from Ron Silver, Idaho from H C. Wainwright. Your line is open.

Thanks, very much for taking my questions again, not to beat a dead horse wanted to ask whether you had had any feedback from the FDA as to whether the letter that they spent was.

Vikran: Thank you. Our next question is from Remb, Salvar Ahun, from H.C. Wingright. Your line is open.

It wasn't any way related to any citizen petition they may have and they may have received regarding excess supply.

Raghuram Selvaraju: Thanks very much for taking my questions. Again, not to be the dead horse, wanted to ask whether you had any feedback from the FTA as to whether the letter that they sent was in any way related to any citizen petition they may have received regarding AXSO5. We have not been made aware of any details related to the deficiencies. We don't know what they are or um or what is behind them or what the cause is. As soon as we learn that information, we'll be okay. And then, as a follow-up to that, do you anticipate that you will be able to arrange a meeting with the FDA or obtain more clarity regarding these deficiencies before the scheduled PDFA date, or do you anticipate that this is likely It's hard for us to speculate what they might be.

Okay.

Yeah.

Yes.

We have not been made aware of.

Any details related to the deficiencies we.

And we don't know what they are or.

And.

Or.

What is what is behind them and what the causes so and <unk>.

Soon as we and as soon as we learn that information and we'll let you know.

Okay, and then as a follow up to that do you.

You will be able to array.

Arrange a meeting with the FDA or.

Obtain more clarity regarding these deficiencies before the scheduled could do per day or do you anticipate that this is likely to already be scheduled app and look to do predict.

It's hard for us to speculate.

Aereotabuto: As you can imagine, our goal right now, with time running out on the Purduefe o'clock, is to learn the nature of the deficiencies as quickly as possible, with the goal of addressing them, and now whether or not, you know, we're given that information or granted meetings, that is not within our control, but that is something that obviously we're trying to do, and we'll let you know as soon as we get any information Okay, and just to clarify what the potential scenarios might be, one scenario is that the drug gets approved by Padoofidate.

You can imagine our goal right now with time spent on the <unk> o'clock is to learn and the nature of the deficiencies as quickly as possible and what.

The goal of addressing them and.

And now whether or not we're.

We're giving that information or rented meetings and all that is not within our control.

That is something that obviously, we're trying to do.

And and we'll let you know as soon as we get any information on.

And as soon as there are any other developments.

Okay, and just to clarify what the potential scenarios might be.

1 scenario is debt.

And it gets approved by the <unk> date, another scenario that the predominant basis.

Aereotabuto: Another scenario is that the Padoodepidate is extended by some period of time, yet to be determined. And yet another scenario is that there is a complete response letter, and then you would have to go through the resubmission process. Is that correct? Those are the possibilities. Okay, and then just very quickly on the Merit Study, I just wanted to know if you had some more detailed thoughts on the prevention of relapse over the six-month time frame that was reported, how significant this finding is, and how differentiated this could make AXS05 within the TRD context.

Standard by some period of time, yet chairman and yet a third scenario is that there is a complete response letter and then you would have to flow through the resubmission process is that correct.

Those are the possibilities.

Okay, and then just very quickly on the Merit study.

Wanted to know if you had some more detailed thoughts on the perfect fair enough relapsed over the 6 month time frame that.

That was reported how significant this finding is and how differentiated this could make a excess of 5 within the TRT context.

Aereotabuto: Well, we think it's a very important finding. A lot of companies actually do not, in relapse prevention studies, do not actually have relapse prevention as, as one of the endpoints because it may be the drug may work and delaying relapse, but it's another thing to actually prevent relapse. So that is a higher bar. So we think it is very relevant as, As Laurie mentioned, it also speaks to the durability of activity of the drug, as a reminder, patients prior to enrollment into merit, had been on drugs, some of them for as long as 12 months, and then they were randomly discontinued, So they either remain on XS-O-5 or they discontinued XS-O-5, for another six to nine months, So that's a very long period of time to demonstrate durability of the products. So the fact that none of the patients relapsed.

Well.

We think it's a it's a V.

Very important finding.

And.

A lot of companies actually do not in relapsed revenge and studies do not actually have relapsed prevention as.

As 1 of the endpoints because it maybe.

And the drug and May work and delaying relapse.

But it's another thing to actually prevent relapse, so that debt that has a higher bar. So we think it is irrelevant.

And as Lori mentioned.

It also speaks to the durability of activity of the drug as a reminder, patients prior to enrollment into merit had been on drug and some of them for as long as 12 months.

And then they were.

Random randomly discontinued.

So they either remain on excess will 5 or they discontinue the excess was 5.

For another 6 to 6 to 9 months at least so.

That's a very long period of time to demonstrate durability of the products. So the fact that none of the patients relapsed.

Aereotabuto: Thank you. Our next question is from Joseph Stone with Gowan and Company. Your line is now open. Are there?

And is significant.

Thank you.

Thank you. Our next question is from Joe SaaS Zone.

Joseph John: Hi, there, good morning, and thank you for taking our questions. Just a little point of clarification, based on the kind of timing of the notification from the FDA, had you submitted any additional information to them? I think, Ariel, maybe you mentioned you provided sort of the top line results of merit. Is that correct? And maybe how long would it take to kind of scrub the data to give it to them in a more thorough fashion if that's necessary?

Cowen and company. Your line is now open.

Are there and good morning, and thank you for taking our questions just a little point of clarification based on.

And the timing of the notification from the FDA and have you submitted any additional information to them and I think maybe you mentioned you provided sort of a top line results with more of it.

And is that correct and maybe how long would it take to kind of scrub the data to give it to them and they.

And more thorough fashion, if that's necessary.

Aereotabuto: And then the second point, is AXO7 manufactured in the same facility as AXO5? So I'll take the first question and then I'll let Mark answer the second question. So with regard to the merit data, as I mentioned, you know, we received the data over the weekend. We have made the agency aware of the top line results in the study. If they request additional data, we are prepared to provide it. So, hey Joe, it's Mark.

And then the second point.

And the access of southern manufactured and our same facility is X and so forth.

So I'll take the first question on and then I'll, let Mark answer the second question. So with regards to the merit data.

As I mentioned, we received the data over the weekend, we have made the agency aware of the top line results from the study if they requested additional data we are prepared to provide it to them.

So hey, Joe it's Marc so.

Mark L. Jacobson: So for the manufacturing process for AXSO7, that actually is a bit more complicated, and there are two facilities that we utilize for the manufacture of the drug product. The APIs are also available under OpenDMFs here in the U.S. And of the two facilities that we use for drug product manufacturing, one of them is the same that we use for AXSO7. Okay, great, thank you. And maybe just one more on the merit data that is a compelling result for the patients in the research to see where it did relapse.

For the manufacturing process for a sense of 7 and that that actually is a bit more complicated and there are 2 facilities.

And that we utilize for the manufacturer of the drug product that drove the Apis are also available under open DMF here and the U S and of the 2 facilities that we use for drug product manufacturing 1 of them is the same that we use for access and 5.

Okay, great. Thank you and then maybe just 1 more on the on the merit data on that.

And as a compelling result, and the patients in the placebo relapsed on how quickly those machine.

Mark L. Jacobson: How quickly was this seen? Is it pretty rapidly, or is it towards the end of the six-month-haul period? Kind of an additional detail we can go out on that would be how. Yeah, so we will be presenting the full result at the conference, so we look forward to providing you with all of the data there, including the relapse curse, so the Kaplan Meyer curse, which will provide some of that information. All right. Thank you very much.

Is it pretty rapidly or was it towards the end of the 6 month policy rate cut.

And efficient.

And he told me going on that would be on coal.

Yes so.

We will be presenting the full results and.

Scientific conference. So we look forward to providing you all of the data there and including the the relapsed or so the Kaplan Meier curves, which will provide some of that and information.

All right great. Thank you very much.

Joseph John: Thank you. Our next question is from June Lee with Truist Securities. Your lines, okay? Hi, thanks for taking the call.

Thank you. Our next question is from Joon Lee with <unk> with <unk> Securities. Your line is open.

Joon So Lee: Hi, thanks for taking out the question. So at this point, you know, given the producer, it's just a couple of weeks away, do you think the most likely outcome is a CRL? And is that when you would find out what the deficiencies are? Just curious, what you think is the most likely outcome.

Hi.

Thanks for taking our questions.

And so at this point given the produce price just a couple of weeks away do you think the most likely outcomes with BRL.

And is that why you would find out what the deficiencies are just curious.

And what what you think is the most likely outcome and then.

Joon So Lee: And then another question on CMOs: is there a strategic reason for not disclosing who the CMO is? We've seen companies, you know, who disclose who the CMO is, and others who choose not to disclose who the CMO is. Just wondering if that's based on any strategic or competitive advantage of not disclosing versus disclosing who the CMO is. Thank you.

Another question on CMO is there a strategic reason for not disclosing who the CMO is we've seen companies who disclose through the CMO is and others, who choose not to disclose who the CMO and just wondering what.

And that's based on any strategic or competitive advantage of not disclosing versus disposing flu this year.

Yes.

Aereotabuto: Yeah, I'll turn it to Kevin, who will answer your first question. And with regard to disclosing who our vendors are, that is something that we typically do not do. Different companies have different policies, but that is all policy.

Yes, so I'll turn it to Kevin who will answer your first question and with regards to disclosing who our vendors are and that is something that we typically do not do different companies have different policies, but that that is all policy Kevin.

Aereotabuto: Sure, you know, I've mentioned earlier there are a couple different potential actions that could occur between now and the Padofa date. You know, we still have time. Two weeks remain until Padoofa, and there is a possibility that approval is possible if labeling the good things can proceed. There is also a possibility that, if the Padupa data is extended, for example, the merit data is relevant for their review. Then the third option, as mentioned, is a complete response letter.

Sure.

Mentioned earlier, there are a couple of different potential actions that could occur between now and I do per day.

We still have time 2 weeks remaining until farooq, but there is a possibility that approval is possible labeling and.

You can proceed.

And there is also a possibility that the.

And the Paducah date is extended if for example, the merit data is relevant for their review.

And then the third option and as mentioned a complete response letter.

Aereotabuto: And really, based on what we know today, which is that we don't know what the deficiencies are, those are the options that are available to the agency at this point. You know, maybe a quick follow-up. You know, you know, he... Are there any obligations by the FDA regarding the level of disclosure and interaction with the sponsor companies? You guys, in terms of communicating, you know, what those deficiencies are and steps to facilitate the resolution of those deficiencies?

And it really based on what we know today, which is we don't know what the deficiencies are and those are the options that are available to the agency at this point.

And maybe a quick follow up.

Yeah.

Are there any obligations by the FDA regarding the level of disclosure and interaction with our sponsor companies you guys in terms of communicating what those deficiencies are and the steps to facilitate the resolution of those deficiencies and I know the times are very tight given that again produced there's only 2 weeks away, but just curious what you are.

Aereotabuto: I know the times are very tight, given, you know, again, the producers are only two weeks away. But I was just curious what you or the FDA could hope to achieve in those two short periods. Yeah, so we can't comment on any kind of internal guidelines that the agency has, but we certainly are trying to learn what the deficiencies are, and it's not curiosity on our part; it's with the goal of addressing them.

And the SBA can hope to achieve and those 2 short periods of time periods, yes.

Yeah.

And we can't comment on any kind of internal guidelines that the agency has.

But we certainly are trying to learn what the deficiencies are.

And it's not curiosity on our part.

With the goal of addressing them.

Thank you.

Okay.

Thank you. Our next question is from <unk> <unk> with Guggenheim Partners. Your line is open.

Yatin Suneja: Thank you. Our next question is from Yatine Sunija with Guggenheim Partners. Your line is open.

Aereotabuto: Hey guys, a couple questions for me, just clarifying. So I think these are understanding that FTA doesn't engage with a sponsor after such a letter is issued because of the legal implications, but it seems like you are implying that you have reached out to them, and there might be some engagement. So can you clarify, did you hear anything from the FTA since that letter was received? Hi, so what we've shared with you is that, clearly, since we got the letter, we've reached out to the agency to try and learn what the deficiencies are.

Hey, guys.

Couple of questions from me and just clarifying so I think it is on understanding that FDA doesn't engage with a sponsor after such a letter that was issued because of the legal implication, but it seems like you are implying that you have reached out to them and there might be some engagement. So can you clarify did you hear anything from the FDA as soon as that leather has been.

And has been received.

Hi yard and so would we.

And what we've.

Shared with you is that.

Clearly since we've gotten the letter.

We've reached out to the agency to try and learn what the deficiencies are and and.

Aereotabuto: And in response, what the agency has informed us is that the review is still ongoing, and no final decision has been made on the review. And so, obviously, we still want to know what the deficiencies are so that we can address them. And once we know it, we'll let you know. Okay, and then the other question is with regard to the launch, like the three you said, you know, if approved, three months after that, you will be ready. Like, what's the gaining factor?

In response.

And the with the agency as informed as Bob is that the review is still ongoing.

And at no point no final decision Hasnt been made on the review.

And and.

So we obviously still want to know what the deficiencies are so that we can address them and once we know.

And we'll let you know.

Okay and then the other question is with regard to the launch of the Dream and you said you know if approved for the month.

After that you will be ready line, what's the gating factor.

Yes.

Aereotabuto: Yeah, given that this is our first launch as a company, there are, you know, just general administrative hurdles that we have to clear prior to being able to distribute the product. And so that's the only reason.

Yeah, so given that and this is our first launch and the company. There are just general and administrative hurdles that we have to clear prior to being able to distribute the product.

And so that's the only reason for that that line.

Lori Englebert: Okay, and could you guys give any update on the narcolepsy study that's ongoing, and then the agitation study, what the status is in terms of enrollment and so with regard to the narcolepsy study, we are on track to initiate a phase three trial with that program this quarter. So stay tuned for that. And with regard to the Alzheimer's disease agitation trial, enrollment there is going as planned. We are nearing 20% enrollment, which puts us on track to complete the study as previously guided in the fourth quarter of 2022. Thank you. Our next question is from Ashwani, Burma, with Bank of America. Your line is open.

Okay and could you guys give any update on the narcolepsy study, that's ongoing and and the and then the agitation study what the status is in terms of enrollment and yep. Thank you.

Sure.

With regards to narcolepsy study, we are on track to initiate the phase III trial with <unk>.

With that program.

This quarter, so stay tuned for that and with regards to the old timers disease agitation trial.

Enrollment there is going as planned we are we are nearing 20% enrollment and.

And which puts us on track to complete the study.

As previously guided in the fourth quarter of 2022.

Got it thank you.

Yeah.

Thank you. Our next question is from.

Suwannee Burma with Bank of America. Your line is open.

Aereotabuto: Hi, thanks for taking our questions. So just the one on AXO5, so I see here in the, in the language in the PR, I think it says preclude discussion of labeling and post-marketing requirements. Are there any other topics that are not precluded? That's my first question. And then the second is on the fibromyalgia drugs.

Hi, Thanks for taking our question. So just 1 on the expense of 5 so I see here and though.

And the language and the PR and I think it changed the picture and discussion of labeling and post marketing requirements on there.

Any other topics that are not precluded.

That's my first 1 and then the second is on the fibromyalgia drugs. So I think you mentioned that it's gonna be filed and posted when he do theirs.

Ashwani Verma: So I think you mentioned that it's going to be filed in 422. There are some pending manufacturing and other activities. Can you elaborate on that a little bit?

And there are some pending manufacturing and other activities can you elaborate on that a little bit. Thanks.

Aereotabuto: So thanks for the questions. With regard to the first question around other topics being that that may be precluded, so the letter specifically is with regard to labeling and post-marketing commitments. That's all it said, so it's hard to interpret it fully without first getting additional detail from the agency. But what we've put in the release is the exact language from the letter, so you can read into that as you wish. With regard to fibromyalgia, the, uh, uh, I'm sorry, what was the question?

So thanks for the questions.

With regards to the first question around other topics being that that may be precluded.

So the.

And the letter specifically with regards to labeling and post marketing commitments to that.

And that's all it said right so.

It's hard to interpret it fully without first.

Getting additional detail.

From the agency, but we've.

Put in the in the releases the exact language from the letter and so you can read into that as you wish.

With regards to fibromyalgia.

The.

I'm sorry, what was the question.

Aereotabuto: Yeah, I'm just trying to understand the, I think you mentioned that there's some pending successful completion of manufacturing and other activities. So I want to understand what is, you know, what needs to be done before it can be filed next year.

Oh, Yeah, just trying to understand I think you mentioned that there is some pending successful completion of manufacturing and other activity volume. So wanted to understand what is oh, what needs to be done before and it can be fine next year.

Aereotabuto: Yeah, sure, I'll, maybe, you know, Kevin could provide some additional details there. But as a reminder, this is a new chemical entity, and so, and so we actually are manufacturing the API and the active pharmaceutical ingredients. So, clearly, we would want to make sure that, you know, we have enough scale to ensure a launch and filing. Kevin, any... additional detail?

Yes sure.

And maybe.

Kevin can provide some.

Some additional details there.

But as a reminder, this is a.

This is a new chemical entity and and so.

And so we actually or manufacturing.

The API.

And and so the active pharmaceutical ingredient.

And so clearly we would want to make sure that.

We have enough scale to to ensure a launch and and finally, Kevin any.

Additional details there yes.

Kevin: Yeah, we need to establish and are starting to establish our own facilities for the production of both the API and the drug product. And, of course, the rate limiter is typically the collection of stability data that would support expiration dating for the product as we file an application. So a lot of it is just waiting for stability data to be accrued before we can file that application.

Yes, sorry.

And we need to establish and are starting to establish or on facilities for the production of both the API and the drug product and of course.

Rate limiter is typically collection and stability data that would support expiration dating for the product as we as we follow on applications. So a lot of it is just waiting for stability data to be accrued before we can file that application.

Okay.

Ashwani Verma: Got it, okay. Thank you. Thank you. Our next question is from Chris Howard and Jeffrey.

Got it okay. Thank you.

Thank you. Our next question is from Chris Howerton with Jefferies. Your line is open.

Chris Howard: Great, good morning, thank you for taking the questions. I think we've had a healthy discussion about

Great and good morning, Thank you for taking the questions.

Healthy discussion on the deficiency letters, so maybe I'll just ask about.

Chris Howard: on the deficiency letter, so maybe I'll just ask about narcolepsy. So, you know, I think you're saying that we're going to have a phase three study soon in the fourth quarter.

And narcolepsy and so I think youre, saying that we're going to have a phase III study soon.

Aereotabuto: So I guess the question is, how do you see the positioning of riboxetine in that setting? You know, I think that there have been some questions as to the significance of the cataplexy and the breakthrough designation that was taken back, I guess, as a result of Wakeicks achieving that label. So I guess, you know, how do you see Roboxetine positioning in narcolepsy, first of all? And then the second question is, with respect to the phase three design, are there any features within that program that you're anticipating that can highlight some of those differentiations?

And the fourth quarter. So I guess the question is is that how do you see the positioning of <unk> and the setting.

And that Theres been some questions as to the significance of the cataplexy and.

And the breakthrough designation that was taken back I guess as a result of wakes achieving that label and so I guess.

How do you see robotic fitting positioning and narcolepsy first of all and then the second question is with respect to the phase III design.

Are there any features within that program that youre anticipating make and highlight some of those differentiations and thank you.

Aereotabuto: In terms of the positioning of AX12 in narcolepsy, it's important to remember that this is still an area of high unmet medical need. So with Petolocent now also having a label for cataplexy, that means that you only have two products that are approved to treat cataplexy, the other one being the oxivate salts. So, still an area of high medical need where most products are still scheduled and where most patients are not adequately treated.

In terms of the positioning of excess 12, and narcolepsy, it's important to remember that this is still.

Free of high unmet medical need and so.

With.

With <unk> and now also having a label for cataplexy.

That means that you only have 2 products that are approved to treat cataplexy and the other 1 being the oxalate and salts, so still and area of high unmet medical need where most products are still scheduled and.

And and where most patients.

<unk> are not adequately treated.

Aereotabuto: So we, uh, looking at AXS12, the product profile is that not only did it have profound effects on cataplexy, which were rapid in onset, but it also rapidly impacted, positively, positively, excessive daytime sleepiness, so not just the fact that it is addressing those two key symptoms of narcolepsy but also the speed of onset. Another important point of differentiation is that we did show an improvement in cognition, which is a symptom complex that is very important to patients with narcolepsy and which is not targeted by other products.

So we.

Looking at.

<unk> 12, the product profile is that not only did it have profound effects on cataplexy, which were rapid onset.

But it also rapidly.

Impacted positively and excessive daytime sleepiness so.

Social and not just the fact that he is addressing those too.

Key symptoms of narcolepsy, but also on the speed of onset.

Another important point of differentiation is that we.

We did show an improvement and cognition, which is.

A symptom complex, which is very important to patients with.

And with narcolepsy.

And and which is not targeted by by other products and in our phase II concert trial, we did show.

Aereotabuto: And in our phase two concert trial, we did show a rapid and highly statistically significant improvement in the ability to concentrate. As you can imagine, all of those endpoints would be studied in our base three program, and we'll look forward to starting that trial, order.

Rapid and highly statistically significant improvement and the ability to concentrate.

And imagine all of those endpoints would it be studied in our phase III program and.

And we look forward to starting that trial in short order.

Okay. That's great. Thank you very much.

Chris Howard: Thank you. The next question is from Matt Kaplan with Leidenberg-Talman, Yolene Zouk.

Thank you. The next question is from Matt Kaplan.

And Ladenburg Thalmann. Your line is open.

Matthew Lee Kaplan: Hi, good morning, and thanks for taking the questions. I guess beyond the pivotal studies and long-term safety studies, he talked a little bit about the ancillary studies that were part of the NDA. Did you have to complete likeability studies and drug-drug interaction studies? Were those part of your package as well?

Hi, good morning, and thanks for taking the questions.

Just wanted to 2 <unk>.

A little bit about the deficiency letter I guess beyond the pivotal studies and long term safety studies and you talk a little bit about the ancillary studies that were part of the NDA did you have to complete Likeability studies or.

And drug drug interaction studies were those part of your package.

And as well.

And.

Aereotabuto: So we did not have to complete likability studies, and then drug-drug interaction studies were definitely part of the package. So the package included actually an array of clinical pharmacology studies, and drug-drug interaction studies would fall into that. And so it was very, complete. Thanks for that. And then, you know, congrats on the merit study results.

So while we did.

Did not have to complete Likeability studies and and drug.

Drug drug interaction studies were definitely part of the package and so the package included accurately.

And array.

Clinical pharmacology studies and.

Drug drug interaction studies would fall into that.

And so it was it was very very full complete package.

Okay.

And then.

Congrats on the merits on your results.

Aereotabuto: Can you talk a little bit about how the durability that you saw after six months compares to some other available treatments for TRD or just MDD in general in terms of the durability that you saw? It's hard to make cross-trial comparisons, but we are very excited by the durability. This is not new.

Can you talk a little bit about how the durability that you saw after 6 months compares and some other available treatments for.

And for CRD, or just MTBE, and and general and terms of durability that zone.

Yeah. It's.

It's hard to make up cross trial comparisons.

But we are very excited by by the durability.

Aereotabuto: I mean, we did show durability, which was very impressive in the comic trial, and their patients were treated for up to 12 months. So not only was there a rapid reduction in depressive symptoms, but it was maintained out to 12 months of treatment. So this is not new information, and what's new is that even beyond that, patients were still stable and did not remit, I'm sorry, did not relapse for an additional up to, you know, potentially, you know, 12 months.

New and we did show.

Durability.

And because very impressive and the combo trial and their patients were treated for up to 12 months. So that not only was there a rapid.

Reduction and depressive symptoms, but it was maintained out to 12 months of treatment.

Okay.

This is not new information and.

What's new is that.

Even beyond that patients were still stable and.

And.

Did not remit did not relapse free.

Sure and additional up to potentially 12 months, so certainly at least 6 months.

Aereotabuto: So certainly at least six months, maybe patients, uh, nine months, and this was in a randomized fashion, so which lends obviously credibility to the data since it is controlled. Thanks, thanks. Thanks, so we had a detail here.

Patients.

9 months and and this was in and in a randomized fashion, so weight, which lens.

<unk> credibility to the data.

It is controlled data.

Alright. Thanks. Thanks, Thanks, so at a detailed line.

Myles Robert Minter: Our next question is from Miles Minter with William Blair. Your line is up. Hey guys, thanks for

Thank you. Our next question is from Myles Minter with William Blair. Your line is open.

Myles Robert Minter: Hey guys, thanks for taking the questions. I'm just wondering in any of your previous interactions with the agency prior to filing, whether they made mention of requiring efficacy demonstration across a broad range of depression patients and not just those that ended up in Ascendant Gemini. Just asking that off the back of the KDSRL where the agency seems to want efficacy across multiple dementia subsets in that DRP board label. And secondly, if that did come up as a deficiency and they were kind of pointing towards stride one being technically negative, could you actually use the target sub-study that you recently presented as a response to that deficiency if it showed up? So the answer is that this has not come up in prior discussions with the agency. And it's hard for us to speculate since we don't know what the deficiencies are. Okay, fair enough.

Hey, guys. Thanks for taking the questions I'm just wondering in any of your previous interactions with the agency.

Product filing whether they made mention of requiring efficacy demonstration across a broad range of depression patients and not just started and the doctor and ascend and Gemini just asking that off the back of the Acadia say, our outweigh the agency sales of 1 efficacy across multiple dimensions subsets and in that day.

Pedro on label.

And secondly, if that did come up as a deficiency and now are kind of pointing towards stride, 1 and being technically negative could you actually use the target sub study that you recently.

And said as a response to that deficiency, if it showed up.

So.

The answer is.

That has not come up in prior discussions.

And with the agency.

And and it's hard for us to speculate since we don't know what the deficiencies are.

Okay.

Okay fair enough and.

Myles Robert Minter: And then maybe just on the response rate of the drug running period that was up to 12 months in Merritt. Was that similar to what we saw in Stride 1, or is that data that you're going to be presenting at a later medical conference? Thanks.

And then maybe just on the.

The response rate of the drug running period that was up to 12 months and in Merit was that similar to what we saw and stride, 1 and or is that day to that you're going to be presenting at a light and medical conference. Thanks.

Myles Robert Minter: That's data that we have to analyze. So when we looked at the comet data, uh, that study included patients not only who had TRD but also included patients with other lines of treatment. And so it was the patients who had TRD, who had TRD and who were, who had TRD and who were in stable remission were randomized into merit. So, you know, we'll have to do some calculations which we can do to provide you the exact answer to that, and we would anticipate providing that then, when the data are fully Thanks for the questions. Thank you. We have our last question from the line of

Okay.

And that's data that we have to analyze.

And when we looked at.

The common data.

So that study included patients not only who had tier D. But it also included patients.

And with other prior lines of treatment and and so it was the patients who had CRD.

Rent wed CRD and horror and stable remission were randomized into merit. So we'll have to do some calculations with which we can do to provide you the exact answer to that and.

And we would anticipate providing that information.

And when the date are fully presented.

Okay. Thanks for the question.

Thank you we have our last question from the line of David Wong with Sbe. Your line is open.

Operator: My line is David Wong with SBE. Your line is

David Timothy Hoang: Hey, good morning. Thank you for fitting me in.

Hey, good morning, Thank you for fitting me in and so it's just a couple of quick questions.

David Timothy Hoang: So just a couple quick questions. So again, I realize this is a little bit of speculation here, but in the event you were to receive a CRL, could you just talk a little bit about sort of what the next steps would be there? Would you, you know, would you look to schedule a type of meeting?

So again I realize this is going to be.

A little bit speculation here, but.

And if you were to receive a CRM.

Can you just talk a little bit about sort of what the next steps would be there would you would you look to schedule a meeting.

Aereotabuto: And, you know, do you think there's anything in the merit study that you could potentially bring forth as, you know, supportive, to be supportive of, uh, the application? So with regard to next steps after a CRL, that is typically requesting a type A meeting. So in that eventuality, that is exactly what we would do, and we would do it, as quickly as possible, and with regard to the usefulness of merit in Under any scenario, it's very difficult to speculate since we do not know what the deficiencies are. Got it, understood.

And do you think there is anything in debt.

The Merit study that you could potentially bring force.

As you have supported that and be supportive of that.

The application.

Okay.

So with regards to next steps after a CRM that.

That is typically requesting a type a meeting so and so.

So in that and eventuality that is exactly what we would do and we would do it and.

As quickly as possible.

And with regards to.

On the usefulness of Merit and.

Under any scenario.

And it's very difficult to speculate since we do not know what the deficiencies are.

Got it understood.

David Timothy Hoang: And then just one on AXS14 for fibromyalgia. So maybe just remind me of this, but if I understand correctly, the molecule originally, the molecule originated with Pfizer, you know; they had been developing it for some time. So, just curious, do you know, as to why Pfizer never, you know, proceeded with filing for approval, and they never sought approval for the drug in fibromyosis? Well, what we can tell you is that it was a decision that was made as part of a portfolio decision, so that was disclosed by Pfizer.

And then just 1 on.

<unk> 14 for fibromyalgia.

And maybe just remind us if I understand correctly the molecule originally the molecule originate with Pfizer.

They had development for some time.

Just curious do you know as to why Pfizer and never.

Proceeded with filing for approval and they never thought and approval for the drug and fibromyalgia.

What we can tell you is that it was a decision which was made.

As part of our portfolio decisions, so that was disclosed.

By Pfizer, but we can tell you that it has nothing to do with it had nothing to do with.

David Timothy Hoang: But we can tell you that it has nothing to do with, it had nothing to do with, the efficacy of the product or the safety of the product. And importantly, that portfolio decision was made before the readout of the positive phase three trials.

And the efficacy of the product or the safety of the product and importantly that portfolio decision. It was made before the readout of the positive phase III trials.

Aereotabuto: Okay, really helpful. Thank you for taking the time to answer my question. Thank you. Since there are no more questions, I will turn the call back to Axom's CEO for any concluding remarks. Well, thank you all for joining us on the call today. We remain committed, as always, to advancing our portfolio of differentiated product candidates for the benefit of patients living with CNF disorder. We will keep you updated on the progress of our NDA for AXO5 as we learn more, as well as on the rest of the pipeline. Thank you.

Okay really helpful. Thank you for taking my questions.

Okay.

Thank you.

Since there are no more questions I will turn the call back to <unk> CEO for any concluding remarks.

Well. Thank you all for joining us on the call today, we remain committed as always to advancing our portfolio of differentiated product candidates for the benefit of patients living with CNS disorders. We will keep you updated on the progress of our NDA for <unk>, because <unk> 5 as we learn more.

As well as on the rest of the pipeline. Thank you.

Aereotabuto: This concludes today's conference call. Thank you for participating. You may now disconnect. Have a great day.

This concludes today's conference call. Thank you for participating you may now disconnect have a great day.

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Net income.

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