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, 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 Axsome Therapeutics. Please go ahead..

Thank you, operator. Good morning, and thank you all for joining us on today's conference call. This morning, we issued two press releases. Our earnings press release providing a corporate update and details of the company's financial results for the first quarter of 2022 and the release relating to the FDA's action on the AXS-07 NDA.

These crossed the wire a short time ago and are 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 the source of future clinical trials, regulatory plans, future research and development plans, commercial plans and possible intended use of cash and investments.

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements.

These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned us to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements.

Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Lori Englebert, Executive Vice President of Commercial and Business Development; and Dr. Amanda Jones, Senior Vice President of Clinical Development.

Herriot will first provide an overview of the company and then review recent developments and upcoming milestones. Following Herriot, 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 Herriot..

Thank you, Mark. Good morning, everyone, and thank you all for joining Axsome Therapeutics' first quarter 2022 financial results and business update conference call. The past few months have been incredibly busy and productive for Axsome.

We have made progress in the FDA reviews of both of our NDAs, announced the agreement to acquire Sunosi and continue to advance the rest of our rich late-stage pipeline, which includes AXS-05 in Alzheimer's disease agitation, AXS-12 in narcolepsy and AXS-14 in fibromyalgia.

Axsome is poised to transform into a commercial entity potentially as early as this month, a direct results of our team's focused execution. I will provide an update on the status of our NDAs, the pending Sunosi acquisition and the rest of our pipeline before turning it over to Lori and Nick, who will provide a commercial and financial update.

With regards to AXS-07, this morning, we announced that we have received a complete response letter, or CRL, from the FDA for the AXS-07 NDA for the acute treatment of migraine.

Importantly, the CRL did not identify or raise any concerns about the clinical efficacy or safety in the NDA, and the FDA did not request any new clinical trials to support the approval of AXS-07. The principal reason given in the CRL relate to chemistry, manufacturing and controls or CMC considerations.

The CRL identified the need for additional CMC data pertaining to the drug product and manufacturing process. We believe that all the issues raised in the CRL are addressable. We are excited by the prospects for AXS-07. This excitement is driven by the strong clinical data and product profile of AXS-07.

The approval of AXS-07 would offer a much needed new multi-mechanistic treatment option for the millions of people living with migraine. It is our goal to work closely with the FDA to provide them with the information they need so that we can make this important new medicine available to patients as quickly as possible.

We intend to provide potential timing for a resubmissions following consultation with the FDA. With regards to AXS-05, review of the NDA is progressing. Based on feedback from the FDA, we believe that the previously disclosed CMC deficiencies have been resolved.

In addition, we recently received and agreed the post-marketing requirements and commitments proposed by the FDA for AXS-05. Based on this interaction, we anticipate potential FDA action on the NDA in the second quarter of 2022.

With regards to our Alzheimer's disease agitation program, enrollment in the Phase III ACCORD trial of AXS-05 in this indication continues to progress. As previously disclosed, we are evaluating the design of the study and will provide an update following consultation with the FDA. Moving on to the Sunosi acquisition.

In March 2022, we entered into a definitive agreement to acquire Sunosi or solriamfetol from Jazz Pharmaceuticals. Sunosi is a dual-acting dopamine and norepinephrine reuptake inhibitor indicated to improve wakefulness in adults with excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea.

The Hart-Scott-Rodino waiting period for the acquisition has now expired. And so we expect the transaction to close this month.

Between a pending FDA action on our NDA for AXS-05 in depression and the expected closing of our acquisition of Sunosi, Axsome is poised to potentially make two important new medicines available to patients living with serious CNS disorders in the coming months. The rest of our late-stage pipeline continues to advance.

For AXS-12, our product candidate being developed for the treatment of narcolepsy. Enrollment in the SYMPHONY Phase III trial is progressing and top line results are anticipated in the first half of 2023.

For AXS-14, our product candidate for the treatment of fibromyalgia manufacturing and other activities related to the planned submission of an NDA are ongoing, and we expect to submit the NDA for this product candidate in 2023. I will now turn the call over to Lori, who will provide a commercial update..

Thank you, Herriot, and good morning. The commercial team remains focused on preparations for potential commercial launches and simultaneously have been working hard to ensure a smooth transition of Sunosi into the Axsome infrastructure.

I am extremely proud of the efforts from the entire Axsome team and immediately upon deal close, we look forward to welcoming the Jazz employees to Axsome. Axsome is on the verge of becoming a commercial entity, and we are excited about the opportunity to bring potentially life-changing therapies to patients.

The addressable diseases of focus for our near-term products are highly prevalent and have substantial unmet need. Our products, if approved, will bring a differentiated clinical profile to their respective markets.

As a reminder, Sunosi is the first and only FDA-approved dual-acting DNRI to treat excessive daytime sleepiness in adults with narcolepsy or OSA. EDS associated with narcolepsy or OSA is a serious condition that is associated with impaired neurocognitive function and can have effects on attention, memory and executive functioning.

Narcolepsy is an orphan condition that affects close to 200,000 people in the US, all of whom experienced EDS. OSA on the other hand, is a highly prevalent condition that affects an estimated 22 million US adults, an estimated 75% of OSA patients experienced EDS.

Many of them continue to experience EDS despite the use of continuous positive airway pressure or CPAP. Regarding AXS-05 and major depressive disorder, the mental health crisis impacting the US continues with an estimated 21 million US adults experiencing MDD each year.

And recent studies estimate that number has likely increased threefold due to the COVID-19 pandemic. MDD is a common and serious medical illness that negatively affects how people feel, the way they think and how they act. MDD is also the number one cause of disability worldwide.

Given the personal and economic burden associated with mental health conditions, there's an urgent need to bring support to those affected. If approved, AXS-05 would be an important new treatment option for the many Americans living with depression. We are prepared and ready to commercialize, if approved. Shifting to AXS-07.

Despite recent innovation in the acute migraine market, there continues to be close to 70% of dissatisfaction rate with currently available therapies, demonstrating high unmet need for the 37 million Americans who experience migraine.

Regardless of any delay on AXS-07 due to the CRL, we have been actively preparing for launch and will be ready to do so if approved. Promotional efforts on Sunosi, combined with our near-term planned potential launch for AXS-05 in major depressive disorder allows for a highly complementary sales force efforts.

40% of the current prescriber base for weight-promoting agents is made up of psychiatrists and neurologists are primary targets for AXS-05 and AXS-07. As a reminder, all sales force offers are contingent upon approval. Lastly, our first-in-class digital-centric commercialization or DCC platform remains fundamental to our commercialization strategy.

Our DCC platform was designed to augment our promotional efforts to allow for highly effective, efficient and more meaningful engagement with physicians and patients. The goal of DCC is to meet customers where and how they want to be engaged with the right content at the right time.

Our commercial launch strategy is innovative and purposeful with the intent to bring important new products to the market in a meaningful way. The differentiated clinical profiles of Sunosi, AXS-05 and AXS-07 have the potential to bring significant benefit to patients and the physicians who treat them.

I look forward to discussing in greater detail the commercial plans for AXS-05 upon potential approval and for Sunosi after the close of the transaction. We remain excited about the opportunity to potentially bring these important new products to market in the near term. I will now turn it over to Nick, who will review our financials..

Thank you, Lori, and good morning, everyone. Today, I will discuss our first quarter results and provide some financial guidance. We ended the quarter with approximately $85 million in cash compared to roughly $86 million at the end of the year, a net decrease of approximately $1 million.

During the first quarter, we accessed our ATM facility, receiving net proceeds of approximately $31 million. R&D expenses were $12.6 million for the three months ended March 31, 2022, and $15.6 million for the comparable period in 2021. The decrease was driven by expenses related to the NDA filing, which occurred in the prior comparable period.

G&A expenses were $25.7 million for the three months ended March 31, 2022, and $11.2 million for the comparable period in 2021. The increase was primarily related to pre-commercial activities and personnel expense, along with an increase in non-cash stock compensation expense.

Net loss was $39.6 million or $1.03 per share for the three months ended March 31, 2022, compared to a net loss of $29.3 million or $0.78 per share for the comparable period in 2021. The net loss for the current period includes $7.6 million of non-cash stock compensation expense compared to $3.7 million in the comparable period.

Regarding the Sunosi acquisition, the acquisition is being funded through our existing $300 million facility with Hercules Capital, plus an additional equity investment from Hercules Capital.

We believe that our current cash balance, along with the remaining committed capital from the $300 million term loan facility is sufficient to fund anticipated operations into 2024 based on our current operating plan, which includes the potential launch of AXS-05 in MDD and the acquisition and commercialization of Sunosi.

That concludes our first quarter 2022 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. Our first question is from Charles Duncan of Cantor Fitzgerald. Charles, your line is open..

Hey. Good morning, Herriot and team. Thanks for taking our question. I have a couple of questions, primarily on 07 and then on 05.

Regarding 07 and the CRL, I guess, I know you haven't met with the agency, but can you provide us any additional color on not only this subject, but of this CRL in terms of CMC, but what gives you confidence in your ability to address it? And how related is it if at all, to the CRL or not the CRL, the CMC issues that you received with 05?.

Hi, Charles. Thanks for the question. I'll make some overarching comments and then I'll turn it over to Mark who maybe can provide some more details. With regards to the relationship, the question between 05 and 07, there is no relationship. The issues are distinct.

And then also with regards to 05, we did also announce that the CMC-related deficiencies have been addressed and resolved. Now with regards to the 07 CRL, it's important to reiterate that the CRL did not identify or raised any concerns around the clinical efficacy or safety of the data in the NDA. So we feel very good about that.

And we think that it's great to get affirmation from the FDA at the end of a review with regards to our clinical data. So it's - we love the product. We think it's an incredibly exciting profile, and it's good to get to the end of a review. Now with regards to the CMC questions and considerations, I'll turn over to Mark..

Hey, Charles, good morning. So as we mentioned, the questions and the request for additional information, they principally related drug product and the manufacturing process. So just a reminder that AXS-07 incorporates our MoSEIC technology, with novel technology that Axsome developed.

And so that does increase the complexity of the manufacturing process, the MoSEIC technology. And so we understand the basis for many of the questions, and we do believe they're addressable. And to give you just a little bit more detail. The technology is a molecular inclusion complex buffering system and many of the questions relate to that.

And one other bit of information that may be helpful just to try and address the different elements of your question, is our impression is the facility inspection that we have previously shared that we were informed was required that, that was completed and that there were no findings as a result of that inspection..

So it sounds like really a distinct set of issues relative to 05, but you feel like it's – they're addressable and you'll provide us timing after you meet with the agency.

Do you have a sense of when that could be?.

So that's correct that we – that, that will be an approach we plan to take and how we share with folks. So we want to do that expediently. We do want to make sure we take our time to prepare for the computations and we will do that expediently. And as soon as we have a sense of granularity for timing, we'll let you all know.

And then related to timing, we would expect this to be a Class II resubmission. And so that I think as everyone is aware, that's a six month review..

Got it. And then one quick two-part question on 05, and that is great to hear that you've received some communication from the agency on post-marketing requirements. I'm sure that you can't provide a lot of detail on that.

But I'm wondering if the post-marketing requirements for 05, should it be approved, does that include a REMS? And if so, can you provide any color? And then the second part is, given the kind of changing therapeutic landscape to incorporate perhaps more intermittent treatment, for example, with Serene alone out of Biogen, Sage, their filing.

Do you anticipate there to be the same kind of demand or opportunity set that you had seen when you initiated the program with AXS-05? Thanks..

Sure. Thanks, Charles, for those follow-up questions. With regards to the question around the REMS. REMS was not part of the PMRs or PMCs that we're agreed to or discussed with the FDA.

And just some overarching comments on your question around intermittent treatment before I turn it over to Lori he can - might be able to provide some additional details there. But some overarching comments are that, the way that major depressive disorder is treated have always been intermittent treatment.

So major depressive episodes are treated, of course, and then many patients once they get better and they've been better for a while, clinicians would taper them off to their medications. The important aspect of treatment here is that not only should patients receive a lease from their depressive symptoms, but that, that should be maintained.

So durability is really important. And we've shown significant durability with AXS-05 over a long treatment period. So we treated patients out to one year. So we feel as good as ever if not better about the prospects for AXS-05 in MDD.

Lori?.

Yeah. Hi, Charles. Good morning. You know, there's estimated up to 80 million prevalent MDD patients in the US right now. And as we all know, we're in the middle of the middle health crisis. So any new therapies coming to market, we're excited about for patients and their ability to get treatment.

What we know now with the current available therapies, two thirds do not achieve remission.

And given the clinical profile of 05 with a fast onset of action, the really fast achievement of remission and the durability as Herriot was mentioning, we do believe it is differentiated and compelling for physicians, and we don't see this as hindering our demand at all..

Very good. Thanks for taking my questions. Congrats on the progress..

Our next question is from Joon Lee of Truist Securities. Joon, your line is open..

Hi. Thanks for taking our questions. And thanks for the updates.

So for – on 05, have you started labeling discussions yet?.

Joon, thanks for the question. What we've said is that as soon as we enter into labeling discussions, we will let the Street now..

Great.

And then can you remind us the conditions under which you can draw the Suno funds from the Hercules loan facility? Does it require approval of 05?.

Yeah, sure. So for - upon approval of AXS-05, there is $100 million that is tied to that approval. However, we do have an amendment that we had signed and becomes executed upon the Sunosi transaction. And that will accelerate the later tranches to fund up to $45 million of the Sunosi transaction.

I think it's also important to note that Hercules has also committed $5 million to $8 million in a direct equity investment upon the close of the transaction..

Thank you.

And then last question quickly, the trial amendment that you're contemplating for the Alzheimer's agitation study for AXS-05, is that in any way related to sort of the discussion you're having with the FDA with regards to the depression indication?.

No. It's not related to that..

Thanks for the questions..

Our next question is from Vikram Purohit of Morgan Stanley. Vikram, your line is open..

Great. Thank you for taking my questions. Two on the pipeline from our side. The first, staying on the topic of the ACCORD study. So you did mention previously that relapse events have been below your potential projections.

So I just wanted to see if you could give us an update on how those have been trending since you last provided us an update? And then also, do you have any sense of timing at this point on when you might be able to speak with the FDA about amendments to the study design that you might have in mind?.

Sure. I'll let Amanda take that question..

Sure. Thank you. Regarding the rate of relapses currently, so we have not disclosed any numbers, and we will disclose it when we provide top line data towards this study. And in regards to the timing of discussion with the NDA, we haven't provided any granularity, but we do intend to do so soon as possible..

Okay. And as a follow-up, for AXS-14 in fibromyalgia, I know you've guided to an NDA submission in 2023.

What needs to happen between now and then for that NDA submission? And do you know specifically one in 2023 that might be expected? Is it more the first half event or second event?.

Hi, Vikram. It's Mark. So we haven't given granularity on the timing yet for 2023. As we get closer, we'll narrow that guidance for you all. And right now, the rate limiting step is - continues to be the manufacturing and stability. We do have to recapitulate and are - the manufacturing from the prior process and that work is ongoing..

Okay, understood. Thanks..

Our next question is from Marc Goodman of SVB Leerink. Marc, your line is open..

Yes. Good morning. Herriot, I think I heard you say that you have affirmation with respect to 07 that there is nothing else related to efficacy or safety.

Can you make that same comment when it comes to 05?.

It's impossible for us to make any comment like that with regards to 05 prior to an NDA action. So we're able to make comments with regards to 07 because now the review is officially completed, and the FDA has formally provided us, with the determination that the NDA is completed and what the outstanding issues are.

So with regards to 05, while we are very positive with - on the efficacy profile and on our package. And while we are encouraged by the latest developments in the review process with the PMRs and the PMCs, we - as you can understand, it's not over until we get the FDA action, and we're very much looking forward to the FDA action hopefully, soon..

Yeah. And just on 05, there seems to be just a concern out there that that there could be a problem with how this thing gets labeled. I assume it's because of the dextromethorphan component. You mentioned specifically that there will be no REMS, so that's great news.

Are there any other issues that seem to be out there with the FDA regarding dextromethorphan? Or you don't think that's going to end up being a labeling issue at all?.

Well, all we can speak to is our product. And just as a reminder, the technology is with AXS-05 is we're using metabolic inhibition to inhibit the metabolism of dextromethorphan.

So therefore, the pharmacology is going to be different, which is why the FDA did require us to conduct a very large open-label safety extension study and also to have exposure in thousands of patients. So we've done that, which is fantastic. We're confident in the data.

We released those data, and we're looking forward to the conclusion of the review and the NDA action..

Okay. And then lastly, just on a big picture manufacturing. Obviously, it seems to be a discussion here on just about every product. Can you just remind us, are you using the same manufacturing companies with respect to all of these products of 07, 05, 14? I mean are we going to have the same kind of issues or what? Thanks..

There is some natural overlap, as you can imagine, amongst vendors. However, we do not think that the issues related to one NDA versus the other or related at all in any way.

And then the other thing that I mentioned - sorry, the other thing that I would mention, too, is while this is - while it is disappointing, obviously, to get to the end of a review and have a CRL, there does seem to be just more globally, if you look at the industry, an increase in the percentage of NDAs that receive CRLs, especially for manufacturing that may be an indication of the climate at the FDA.

But for example, the rate of CRLs has been roughly 50% at least in the first half of - so far this year compared to around 15 - 15% historically, and most of those are related to CMC. So we fully understand the reasons why the agency would want to make sure that any new technology, any new manufacturing process is fully vetted..

Well, you're working on manufacturing right now for 14. So it just kind of ends the question of are you learning some things from the issues before? Is this the same manufacturing people who will learn from what the FDA needs with these other products? That's really the question..

Hey, Marc, so each program, we have selected CMOs that we think are best suited to commercialize the product candidates. And so AXS-14, that's an entirely different - that has its own facility, its own companies, API and drug product with AXS-07, there are multiple facilities involved there.

As we mentioned, one of them had a required inspection and our understanding that there were no findings. So this question about - is there an underlying issue with the CMO. We're not aware that that's the case. And there is some overlap with the programs, but generally, each is distinct in then..

Yeah, another way of answering your question, Marc, is yes, there are learnings from every interaction with the FDA from every NDA. And by the time that we file the NDA for fibromyalgia, we would have gone through at least two, maybe three NDA filing. And we will take every lesson that is possible.

We'll mine those experiences to make sure that we increase our probabilities of success in the future..

Thanks..

Question is from Vamil Divan of Mizuho Securities. Vamil, your line is open..

Great. Thanks for taking my questions and for all the info today. So maybe just a couple of separate questions. So one on 05, I think we still got a lot of questions from investors on sort of the payer dynamics here since there is sort of two old new products.

Obviously, we're still waiting for a little approval here, but I'm wondering if you can give any sort of updated thoughts on kind of how you think payers will respond to this product and sort of what sort of hurdles that patients have to go through before they can get on to the product.

And then for Sunosi, just had a question there on - I know you're probably somewhat limited what you think may before the deal officially closes. But I mean your expectations for sort of $1 billion product here are quite a bit above what the Street has generally thought of this product.

I assume it's because the sort of newer indications that you're looking to move this product into. I'm just wondering if there's any more you could share at this point in terms of how you open to expand this product out into other indications beyond what it's already approved for? Thank you..

Thanks, Vamil, for the question, actually, there were two. I'll take the Sunosi question and before turning it over to Lori to take the payer dynamics question on 05. Yeah, we're really excited about the Sunosi acquisition. We did put out an 8-K this morning announcing with the HSR, waiting period has now expired.

So we do expect the transaction to close very shortly.

And we do anticipate having some kind of investor forum to discuss what the new indications are and what we - the timing of that, the timing of making sure that we take the steps that we need to take to get to that $1 billion plus market potential, which we outlined when we first announced the signing of the acquisition.

So we're really excited about Sunosi. And I'll turn it over to Lori to talk about the payer dynamics and to add anything more that she may want to add about Sunosi..

Sure. And thanks for the question. So we started payer - permitted payer discussions back on 05 about a year ago and nothing's changed. Payers continue to recognize the unmet need in MDD, and they continually express their - their understanding of the fact that AXS-05 will bring a novel mechanism of action to market.

They recognize that there's a need for fast and rapid onset of action and also durability for those patients. And we look forward to telling you more once the potential approval comes, and we engage more with it. In terms of Sunosi, we are excited about the current indication as well.

We do believe that there is incredible untapped potential in the current indication for EDS, especially with narcolepsy or OSA. We're also really excited about how the Jazz team has - that will come over to Axsome, have been working during this transition period.

Last week, in fact, MDRX is so new to brand, prescriptions were the second highest of the year, and that came during a time of transition. So we are really excited about the caliber of Jazz employees coupled with Axsome and look forward to welcoming them on the deal close..

Okay. Thank you..

Our next question is from Joseph Thome of Cowen & Company. Joseph, your line is open..

Hi, there. Good morning and thank you for taking our question. Maybe just on the AXS-05 review. It's been a couple of weeks now almost, I think, since you announced that you agreed to the post-marketing commitments.

I guess in the interim, do you continue to interact with the FDA? What's sort of the cadence of interactions around this? And I guess, during that discussion, were you able to kind of find out maybe what the initial deficiencies noted in the July letter last year happened to be? Thank you..

Thanks for the question. As you can imagine, during this phase of the NDA review, there are multiple interactions. So those continue. And with regards to the initial deficiencies, all we are aware of or what the deficiencies are that have been communicated to us, and those deficiencies were CMC.

And as we've stated, we have addressed those deficiencies, and they are now resolved, and we've not been made aware of any other deficiencies..

Great, thank you. Maybe just one follow-up. How are you thinking about Europe? And obviously, you'll get to those here hopefully in the third quarter.

Is that something that you want to launch yourself? And when you think about AXS-05 and AXS-07, how far do you want to take those in discussions with Europe before in a decision on marketing? How are you thinking about that overall?.

The way that Sunosi factors into our European strategy is now it gives us an additional product in Europe, a product which is approved and marketed currently in Europe and which has also a rollout in multiple new European markets on the roster.

So as it relates to our overall corporate strategy prior to the Sunosi acquisition announcement, which was to out-license our product candidates outside of the US. This only puts us in a much stronger position. And as you can imagine, that might lead to greater interest from potential partners..

Great. Thank you very much..

Our next question is from Ram Selvaraju from H.C. Wainwright. Ram, your line is open..

Thanks very much for taking my questions. Firstly, I just wanted a clarification regarding the time line for potential approval of AXS-07. Since you mentioned that this is likely to be considered a Class II resubmission.

Is it appropriate for us to assume at this juncture that the earliest AXS-07 could be approved in the US would be in 2023?.

So Ram, thanks for the question. What we're looking to do is to meet with the FDA as expeditiously as possible. That's a Type A meeting. We want to make sure that we get our ducks in a row prior to requesting that meeting and getting a date. Once we have that meeting and we get feedback from the agency.

In other words, we confirm exactly what it is that should go into the resubmission that we can have success, then we'll be in a position to provide you with updated guidance on timing.

Apart from what we've already said, which is that we do expect that once we resubmit that the resubmission would likely be treated as a Class II resubmission, leading to a six-month review..

Great. And then just two very quick additional ones for me.

Can you comment on how you anticipate deploying the Sunosi sales force that is coming over in the Jazz acquisition transaction? And if you anticipate a meaningful role for those sales representatives in the ultimate promotion of drugs like AXS-05 and AXS-07? And then also if you could comment on any plans that you may have with respect to deployment of either Sunosi or AXS-12 in the area, specifically of idiopathic hypersomnia? Thank you..

So taking those backwards with regards to the additional indications that you mentioned, we are always thinking about additional indications with regards to the specificity. We don't have any specifics to share with you right now. And I'll turn it to Lori to comment on the sales force question..

Hey, Ram, thanks for the question. So I think it's very important for sales forces, especially during launch periods. And in this case, for Sunosi potentially viewing this as somewhat of a re-launch coming over to us. They need to stay focused on their priority targets.

And so they will be deployed to high-prescribing, high-potential, high-value prescribers in the market's, you know, respected markets, the AXS-05 sales force, we'll primarily focus on those targets. Related to AXS-05, where we believe we will have the highest potential and the same for the Sunosi.

However, we do know that there is a very high overlap between prescribers and as appropriate, we will leverage those synergies..

Thank you..

Our next question is from Jason Gerberry from Bank of America. Jason, your line is open..

Hi, guys. Thanks for taking my questions. One clarification. Just in terms of REMS, is that something that you learn about via label discussion? Or is it more something that you learn about what the post-market requirements? And then there's been some recent neurocyte launches that have exceeded their investor expectations.

So I'm just curious if you think there's read across caused effectively, is there any structural challenges at all contracting cycles? Thanks..

Sure. Yeah. Just with regards to the question on the REMS, this is - this is one of the first NDAs actually. These are our first two NDAs that we are going through. REMS is not anything that we were thinking would be needed with regards to these product candidates. You never know, though. And until the review is over.

We can't really assure you of the FDA's findings or decisions or more requirements. But we can communicate to you are the PMRs and the PMCs, which we have agreed to and which have been communicated to us. And they have not included of the REMS.

Lori?.

Jason, sorry, your second question kind of faded in and out.

Would you mind repeating that question?.

Yeah. expectations. So curious if you think there's read across AXS-05 from what you're seeing, it seems like maybe payer coverage is coming online a little faster than expected. I mean, you guys will have effectively a mid-year launch.

I don't know if that will be like a 2022 challenge in terms of where you're at in the contracting cycle or non-issue?.

Yeah. Great. Great question. Thank you. We will - all we have with the committed payer discussions that we've had thus far and that we are highly encouraged by how the payers are reacting to a product profile of AXS-05.

So once we get approval and we know the timing of that approval, we'll be happy to discuss more around what we expect from a payer coverage standpoint then..

Yeah. And if I may add to that, Lori. I think just part of Jason's question related to the broader environment in neurocyte as it relates to recent launches, recent neurocyte launches, which have exceeded expectations and is there something broader going on.

It's hard to know if the performance of individual product launches, even though they coincide in time, reflecting anything that's underlying. There is one underlying trend, which is worth repeating, which is that we are in the middle of a mental health crisis. So there has been an increase, a significant increase in neurocyte disorders.

We think - scientists think that it's related to the COVID pandemic. So that is one backdrop that has been occurring. We know that that's the case, for example, in depression, certainly, but not just in depression, but even across, for example, migraine, the incidence of migraine has gone up in patients who have experienced COVID-19.

So there is that aspect to it. And I think what it speaks to more broadly is the high unmet medical need in neuropsychiatry indications in general. That's why Axsome is a CNS-focused company, and that's why we're really excited about what we're doing..

Got it. Thank you..

Our next question is from Yatin Suneja from Guggenheim. Yatin, your line is open..

Thank you. A few clarification questions for me. So first is on AXS-05.

What are your expectations for labeling? Do you expect the box warning similar to what we see with wellbutrin or other antidepressant?.

So we - since bupropion is a component of AXS-05, we would expect that aspects of the program label would be reflected in the 05 label..

Okay.

And then when you say that this is again related to 05, so when you say that the CMC issues have been resolved, did you get an acknowledgment from the FDA that they are satisfied with your response? Or it has been resolved just that you have submitted the response? Just trying to get a little bit of clarity here, what does the reservation mean here?.

It's pretty clear to us that that is been resolved based on the communications and also the PMRs and the PMCs..

Okay. And then finally, how quickly you might be able to launch once approved for 05? Thank you..

Yeah. Hi, Yatin., we expect to launch within a quarter of approval..

Any comment on the pricing? How should we think about pricing? What work you've done? Any sort of recent comp for us to look at in terms of the price?.

Yeah. We haven't communicated price yet, and we will do that upon approval when we announced price. We expect to price - this product to recognize the clinical differentiation of the product, but we also have an eye towards providing patients with the approach of appropriate access..

Okay. Thanks..

Our next question is from Chris Howerton of Jefferies. Chris, your line is open..

Great.

Really appreciate you taking all the questions this morning and all the extra info So I think for me, I was just curious if you could provide any comments or color on how the 05 approval and launch plays into your current stated cash runway? And as a sequela to that, if there was a delay or non-approvals for 05, how might that affect your cash runway guidance? Thank you..

Yeah, sure. Thanks, Chris, for the question. So again, upon 05 approval, there is $100 million tied to that approval with our Hercules facility. So we feel that we are in a very good position to launch the product. And we are planning that for this quarter. We do have sufficient cash for over a 12 month period.

And as I stated in the opening remarks, we did tap our ATM facility in Q1 for upwards of $31 million to bridge the delay in the approval….

Okay. And maybe just as a quick clarification.

If there was a further delay to 05, how might that affect your current kind of cash runway guidance?.

So if there's a further delay, we'll reassess it at that time. But as I said earlier, we do have north of 12 months of cash on hand to fund our current operating plan..

Okay. All right. Thanks so much. Appreciate it..

Our next question is from Matt Kaplan of Ladenburg Thalmann. Matt, your line is open..

Thank you. Good morning. Just wanted to have a little more detail perhaps on the AXS-07 CRL.

Beyond CMC questions, was there anything else detailed in the CRL that needs to be addressed?.

Matt, so principally with all CMC, there was one item related to non-clinical, which was just our quest for additional information, which we believe we can provide. So for us, the real focus is this is a stand focus is CMC..

Okay, very good. Thank you. And then, I guess, a question for Lori.

Can you give us some more metrics in terms of how you're thinking about the sales organization as you go into launch several products here in terms of some of the metrics around the size of the Sunosi and dedicated for us and 05 and 07 dedicated sales forces, how they're kind of interact....

Yes. sure. So a couple of things to keep in mind as you think through how we plan to structure. We haven't revealed the size of the sales forces yet. But what I can tell you is that we plan to target for AXS-05. We plan to target at least 85% of high-value prescribers, which is more than 25,000 HCPs.

We will not only have a sales force in place, but we will also intend and also intend to leverage our DCC platform to help ensure that we have optimal reach to those high-value prescribers. For AXS-07, it will be a very similar approach in terms of how we structure the sales force, highly targeted, highly strategic, highly focused.

We plan to have coverage of 50% to 60% of the high-value prescribers slip with 05, I mean with 07. And then on Sunosi, the - virtually all the offers that we extended to the Jazz employees were accepted in that sales force size.

We look forward to talking to you more about on the deal close, but it will be exactly the same kind of structure and decision-making, highly focused on those high-value prescribers to make sure that we get our reach, we will augment with DCC..

Okay. Great. Thanks for that detail..

Our next question is from Bert Hazlett of BTIG. Bert, your line is open..

Yes. Thank you for taking the question A quick follow-up to Matt. And what is the additional ask for information regarding CRL for 07, is that related to MoSEIC technology? Or can you be any more specific with regard to the additional ask? Thank you. Then I've got one or two other..

Hey, Bert, I think we characterize it. I mean, much of it does relate to MoSEIC and the process around that and drug product..

Okay. Then just shifting to a cord for just a second.

What are the goals of the interaction with the agent? What can you do with the study? Is it an issue where you might change the design and study like in powering? What are the goals of the discussions with FDA with regard to evaluating the study design?.

So Bert, the reason why it's prudent to have as much feedback as possible. This is a registration trial. And so we want to make sure that we take the right steps and avail ourselves of the fact that this is a breakthrough therapy designated product to get that feedback..

Okay. Thank you. Just one other for me. Smoking cessation, you talked about a pivotal in Phase II/III later this year. Do you think you can get away with one? Or is that something you're going to do sequentially with regard to two pivotals for smoking cessation for 05? Thanks..

We expect that we would need two pivotal studies. And currently, the plan would be to do those sequentially..

Okay. Thank you. Thank you for taking the question..

The next question is from Myles Minter of William Blair. Myles, your line is open..

Hi. Thanks for taking the questions. Just on the 05 timing guidance that you put out when the PMRs and the PMCs were agreed upon and you said this quarter.

I'm gathering that was based on precedent of some sort, but was that directly communicated to you by the agency that timing? Or was that from your regulatory consultants that from work that you've done? Obviously, the streets seen labeling discussions triggering that one month clock, but just wondering how you've got that clarity from the PMR, PMC stage? Thanks..

So Myles, thank you for that question. Just to be clear, there is no new PDUFA date. So the FDA has not beholden to any particular date. What we try to do is to provide the street with actionable information. So any change in terms of our internal estimates, as quickly as possible. So what - so what drove our statement are the PMRs and the PMCs.

So with regards to those discussions, sometimes there are timing elements tied to those. And so that has allowed us to focus our estimate. But again, this is our estimate, and it's not tied to a formal PDUFA date..

Okay. Thanks. And then just on the PMRs and PMCs. Obviously, not disclosing the nature of them.

But - if we were to look at the guidelines, the FDA guidance documents for antidepressant job development, are they 100% encapsulated in the language in there, so like maintenance dosing studies that might be required post-marketing or safety in certain populations? Or are there certain PMRs and PMCs within those that are - would be net to the product that might not be talked about in those guidance documents? Thank you..

Yeah. So as you can imagine, the PMRs and the PMCs would necessarily incorporate both items that are only required for an indication, which might be included in guidance, as well as items that are specific to the individual product.

What we can say is that the PMRs and PMCs that were discussed and that have agreed to are they are consistent – excuse me, that are consistent with our expectations, and there was nothing surprising. We're happy with them. We do not expect them to, in any way, NPE commercialization of AXS-05 for MDD..

Okay. Thanks for the questions..

Two final questions. Our next questioner is David Hoang from SMBC. David, your line is open..

Yeah. Thanks for taking the questions. Just had one on commercialization and the sales force.

In terms of your digital component there, what's your level of confidence that, that's going to be able to supplement the sales force at the current size that you plan to bring on board? And is this something that you would have a high level of confidence in ore would you consider potentially expanding the number of reps down the line?.

Hey, David, thanks for the question. So our DCC platform, the way that we designed it was really to ensure that engagement with HCPs and patients are optimized, meaning, we have the ability to have efficient promotional efforts, but also effective commercial efforts.

So what I can tell you is that we're not going to sacrifice to not have those effective promotional efforts.

So we believe, based on not only research, physician preference data, historical data of how physicians are engaging, how physicians continue to engage, how patients are showing up at physicians' offices or not, meaning the level of virtual engagement in our target therapeutic areas still remains extremely high.

So we feel very confident in the augmentations that BCC will provide our sales force..

Okay. Thanks a lot..

Our final question is from Esther Hong of Berenberg. Esther, your line is open..

Hi, good morning. So on AXS-07 and the CMC issues, I was wondering, number one, did the FDA find this issue? And then number two, did this occur after the facility inspection? Thanks..

Hey, Esther. So, good morning. I don't know that it's a finding from the inspection, as we mentioned that there were no findings that we're aware of. And our sense is, this is the result of their review during the course of the review cycle. And so that's our impression.

But they didn't give us feedback when they identify these needs for additional information..

Okay, got it. Understood. Thanks so much..

Thank you..

That ends our question-and-answer session. So I would now like to pass the conference back to the management team for any closing remarks..

Well, thank you again for joining us on the call today. We are committed to bringing potentially life-changing medicines to people living with serious CNS conditions. We look forward to updating you over the coming months on our continued pipeline and commercial progress. Have a great day..

That concludes the conference call. Thank you for your participation. You may now disconnect your lines..