Axsome Therapeutics - Q1 2024

Executive Summary

• Q1 2024 net product revenue was $75.0M (+160% y/y), driven by Auvelity sales of $53.4M (+240% y/y) and Sunosi revenue of $21.6M (+64% y/y). Total revenue was $75.0M; net loss was $(68.4)M, or $(1.44) per share, with $331.4M cash on hand.
• Auvelity demand and access improved: ~95,000 Rx (+12% q/q), ~18,000 new patients, and contracting with a second large GPO to expand commercial coverage beyond ~48% (overall coverage ~70%).
• Pipeline catalysts: positive Phase 3 SYMPHONY for AXS-12 in narcolepsy; initiation of Phase 3 PARADIGM (MDD) and ENGAGE (BED) for solriamfetol (topline 2025); NDA plans for AXS-07 and AXS-14 targeted for 2Q 2024.
• Seasonality and the Change Healthcare cyberattack pressured GTN and weekly scripts for a brief period; management reported quick recovery by mid-March and stable-to-growing trends thereafter.
• Stock-relevant narrative: accelerating Auvelity adoption (earlier-line use ~50%), GPO access expansion, and multiple late-stage readouts/submissions in 2H24/2025 are key catalysts for estimate revisions and sentiment.

What Went Well and What Went Wrong

What Went Well

• Strong topline growth: net product revenue +160% y/y; Auvelity +240% y/y to $53.4M; Sunosi +64% y/y to $21.6M.
• Access expansion: executed contract with a second large GPO enabling PBMs under the umbrella to adopt contracted terms; Auvelity remains ~70% covered across channels (~48% commercial, ~100% Medicare/Medicaid).
• Pipeline momentum: AXS-12 Phase 3 met primary endpoint (cataplexy reduction) and improved EDS, cognition, and QoL; Phase 3 initiations in MDD and BED for solriamfetol; AXS-07 and AXS-14 NDAs targeted for 2Q 2024.

Selected quotes:

• “Total net product revenue in the quarter was $75 million… We expect to continue the commercial and pipeline momentum in the balance of 2024.”
• “We believe that our current cash balance is sufficient to fund anticipated operations into cash flow positivity based on the current operating plan.”
• “We just contracted with a large group purchasing organization for a potential formulary of Auvelity…”

What Went Wrong

• Seasonal GTN pressure and cyberattack: Auvelity GTN in Q1 was low-to-mid 50s; Sunosi mid-50s; weekly scripts were down ~30–40% for ~2 weeks during the Change Healthcare incident before rebounding.
• Higher operating expenses: SG&A rose to $99.0M (+33% y/y) on sales force expansion and commercialization; R&D rose to $36.8M on multiple Phase 3 trials and NDA preparations.
• AD agitation timeline extended: ADVANCE-2 completion shifted from 1H 2024 (Q3 guidance) to 2H 2024 (Q4 & Q1 guidance), reflecting evolving treatment dynamics (brexpiprazole adoption).

Transcript

Operator (participant)

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. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Darren Opland, Director of Corporate Communications at Axsome Therapeutics. Please go ahead.

Darren Opland (Director of Corporate Communications)

Good morning, and thank you all for joining us on today's conference call. This morning, we issued our earnings press release, providing a corporate update and details of the company's financial results for the first quarter of 2024. The release crossed the wire a short time ago and is available on our website at axsome.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our investigational agents, our clinical and non-clinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development plans, our commercial plans regarding Sunosi, Auvelity, and our other pipeline products, revenue projections, 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. We are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today are Dr. Herriot Tabuteau, Chief Executive Officer; Nick Pizzie, Chief Financial Officer; Mark Jacobson, Chief Operating Officer; and Ari Nowacek, Executive Vice President and Head of Commercial. Herriot will provide an overview of the company and progress made in the first quarter of 2024, as well as key upcoming milestones.

Following Ari, Nick will review our financial results, then Ari will provide a commercial update. We will then open the line for questions. Questions will be taken in the order they are received. With that, I will turn the call over to Ari.

Ari Nowacek (EVP and Head of Commercial)

Thank you, Darren. Good morning, everyone, and thank you for joining Axsome Therapeutics' first quarter of 2024 financial results and business update conference call. The first quarter of 2024 was marked by strong financial performance for our own market products, which are delivering important and differentiated treatment options for patients living with depression, narcolepsy, and obstructive sleep apnea. Total net product revenue in the quarter was $75 million, representing year-over-year growth of approximately 160%. We will share additional details on our financial and commercial performance later on the call. We also significantly advanced our innovative neuroscience pipeline in the quarter, including announcing positive top-line results for AXS-12 in narcolepsy, advancing AXS-07 and AXS-14 with IND submissions, initiating pivotal trials and new indications with solriamfetol, and advancing and expanding our Alzheimer's disease education program for AXS-05.

We expect to continue the commercial and pipeline momentum in the balance of 2024. I will now provide a brief update on our industry-leading neuroscience pipeline and expected milestones. Starting with our two IND stage products. AXS-07 for the acute treatment of migraines is on track for an IND submission this quarter. Additionally, we are conducting the EMERGE study, a multicenter, phase 3, single group trial evaluating the efficacy and safety of AXS-07 in adults with a prior inadequate response to an oral CGRP inhibitor. We anticipate top-line results from this trial in the second half of 2024. For AXS-14, which we are developing for the treatment of fibromyalgia, pre-submission activities for the IND for this product are near completion. We continue to target submission later this quarter.

In March, we announced that the phase III flexibility trial of AXS-12 in narcolepsy achieved its primary endpoint and significantly reduced the frequency of cataplexy attacks as compared to placebo. AXS-12 also reduced excessive daytime sleepiness severity, improved cognition and reduced overall narcolepsy severity. An open-label safety extension trial for AXS-12 is ongoing, with results expected in the fourth quarter of 2024. We are excited about the potential of AXS-12 to provide a differentiated treatment option for patients and HCPs for this debilitating condition. Moving on to AXS-05, we continue to anticipate completion of the phase 3 ADVANCE-2 trial in the treatment of Alzheimer's disease agitation in the second half of 2024. Today, we announced that we've launched the ACCORD-2 study, a double-blind, placebo-controlled, randomized, controlled trial to evaluate the efficacy and safety of AXS-05 in the treatment of Alzheimer's disease agitation.

This study is similar in design to the completed positive ACCORD-1 trial. In ACCORD-2, the clinical development program will now include four controlled efficacy trials. Importantly, ACCORD-2 further increases the robustness in our clinical program, Alzheimer's disease agitation, without impacting our overall development timeline. Enrollment in ACCORD-2 is very far along, and we expect enrollment completion around midyear... With respect to solriamfetol, our dopamine and norepinephrine reuptake inhibitor and serotonin agonist. In addition to continued commercial performance, we launched the phase 3 PARADIGM trial in major depressive disorder and the phase 3 ENGAGE trial in binge eating disorder in the first quarter. Results from both trials are expected in 2025. We are on track to initiate a phase 3 clinical program in bipolar disorder this quarter.

Solriamfetol is also being evaluated in the FOCUS phase 3 trial in ADHD, for which we continue to anticipate top-line results in the second half of this year. Overall, our innovative neuroscience portfolio encompasses five late-stage, patent-protected product candidates targeting 10 serious psychiatric and neurologic conditions with substantial market opportunities. Each product candidate has the potential to transform the treatment landscape of serious and difficult to treat CNS disorders, which affect more than 150 million people in the U.S. I will now turn the call to Nick, who will provide details about our financial performance. Nick?

Nick Pizzie (CFO)

Thank you, Ari, and good morning. Today, I'll discuss our first quarter results and provide some financial guidance. Total product revenues were $75 million for the first quarter of 2024. This consisted of net product sales of $74.1 million and royalty revenue of $900,000. Total product revenues for the comparable period in 2023 were $94.6 million, which consisted of net product sales of $28.6 million, royalty revenue of $300,000, and $65.7 million in one-time license revenue received from the out-licensing of Sunosi in certain ex-US territories. Auvelity net product sales were $53.4 million for the first quarter of 2024, representing year-over-year growth of 240%. Auvelity net product sales for the comparable period were $15.7 million.

Sunosi net product revenue was $21.6 million for the first quarter of 2024 and consisted of $20.7 million in product sales and $900,000 in royalty revenue associated with Sunosi sales in out-licensed territories. Sunosi net product revenue for the comparable period in 2023 was $13.2 million, consisting of $12.9 million in product sales and $300,000 in royalty revenue. Total cost of revenue was $6.3 million for the first quarter of 2024. Total cost of revenue for the comparable period in 2023 was $7.6 million, which included $5 million in Sunosi licensing transaction fee sharing expense. Research and development expenses were $36.8 million for the first quarter of 2024, compared to $17.8 million for the comparable period in 2023.

The increase was primarily related to the initiation of the solriamfetol PARADIGM trial for major depressive disorder, the solriamfetol ENGAGE trial for the binge eating disorder, the advancement of the solriamfetol FOCUS trial for ADHD, the ongoing trials of AXS-05 and AXS-12, manufacturing costs associated with the anticipated NDAs for AXS-07 and AXS-14, post-marketing commitments for both Auvelity and Sunosi, and higher personnel costs, including non-cash stock-based compensation. Selling, general, and administrative expenses were $99 million for the first quarter of 2024, compared to $74.2 million for the comparable period in 2023. The increase was primarily related to commercialization activities for Auvelity and Sunosi, including sales force and marketing expenses, and higher personnel costs related to organizational growth, including non-cash stock-based compensation.

Net loss for the first quarter of 2024 was $68.4 million, or $1.44 per share, compared to a net loss of $11.2 million, or $0.26 per share for the comparable period in 2023. The net loss in the first quarter of 2024 includes $21 million in non-cash charges, of which the majority is comprised of non-cash stock-based compensation expense. The 2023 comparable period included approximately $62 million in net gain from the Sunosi out-licensing. Q1 typically has a negative seasonality effect on GTN, which we saw in both Auvelity and Sunosi versus the prior quarter. Auvelity GTN discount for Q1 was in the low-to-mid 50s, and Sunosi GTN discount was in the mid-50s.

We ended the first quarter of 2024 with $331.4 million in cash and cash equivalents, compared to $386.2 million as of year-end. We believe that our current cash balance is sufficient to fund anticipated operations into cash flow positivity based on the current operating plan. I would now like to turn the call over to Ari, who will provide a commercial update.

Ari Nowacek (EVP and Head of Commercial)

Thank you, Nick. Axsome delivered solid brand performance in the first quarter of 2024. Auvelity demand trends in Q1 once again outpaced growth rates for the market and branded competitors, with approximately 95,000 prescriptions, representing 12% quarter-over-quarter growth and 206% growth compared to the first quarter of 2023. Nearly 18,000 new patients started Auvelity in the quarter, bringing the total number of unique patients treated with Auvelity since launch to more than 89,000. Our sales team continues to activate new prescribers at a consistent rate, with more than 3,600 first-time Auvelity prescribers in Q1, illustrating strong underlying demand for the product and expanded use among depression treaters in both psychiatry and primary care offices. We're especially proud of this performance in light of seasonal dynamics, which were compounded by the industry-wide Change Healthcare cyberattack.

... Payer coverage was stable in Q1 as Auvelity remains accessible to patients representing approximately 70% of covered lives. As noted in our press release this morning, we just contracted with a large group purchasing organization for potential formulary coverage of Auvelity, laying the groundwork for future increases in covered lives. Pharmacy benefit managers and health plans under this GPO are now able to make coverage decisions for Auvelity based on the contracted terms. With this agreement, Axsome is now contracted with 2 of the 3 largest GPOs for potential coverage of Auvelity. We are very pleased with the strong commercial foundation we have created to support Auvelity performance, including our expanded psychiatry sales team, a recently enhanced sales and marketing campaign, and expansion of digital capabilities to maximize reach to targeted HCPs.

Of note, we observed an inflection in weekly new patient starts, or NBRX, in March, a positive signal of both the impact of our optimized commercial footprint and continued adoption of Auvelity as a go-to treatment option for adults with major depressive disorder. Transitioning now to Sunosi. Total prescriptions were just over 41,000, representing a 1.6% decline versus Q4 2023, and 14% growth versus Q1 2023. Demand in the first quarter was impacted by typical seasonality in the EDS market, as evidenced by the 3% decline observed in the weight-promoting agent market this quarter. Approximately 3,700 new patients started Sunosi treatment during the quarter, bringing the total number of unique patients treated with Sunosi to approximately 68,000 since launch.

More than 400 new prescribers were activated in Q1, resulting in a total cumulative prescriber base of more than 12,600 since launch. Payer coverage for Sunosi in Q1 remained 83% of lives covered across channels. In closing, Q1 was a very positive start to 2024 for both Auvelity and Sunosi, with leading indicators such as trends with new patient starts and newly activated prescribers, reinforcing our confidence that Axsome will deliver strong commercial performance in our second year as a commercial company. We continue to receive compelling feedback from healthcare professionals and patients about the positive impact our products are having in real-world settings, and we are proud of Axsome's growing reputation as a leader in the CNS space that delivers differentiated and impactful products for serious psychiatric and neurological conditions. I will now turn the call back to Darren for Q&A.

Darren Opland (Director of Corporate Communications)

Thank you, Ari. Operator, may we please have our first question?

Operator (participant)

Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. We ask that you limit yourself to one question and a follow-up so that others will have the opportunity to ask questions. You may reenter the queue by pressing star one. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for questions. Our first question comes from Charles Duncan with Cantor Fitzgerald. Please proceed with your question.

Charles Duncan (Managing Director)

Hey, good morning, Ari and team. Congrats on a great quarter and appreciate you taking our questions. I had a commercial question and then one on the pipeline. Regarding the commercial question, I'm not sure if I heard it. Ari was speaking fast. Could you give us a sense of new to brand versus refill rates for Auvelity? Thanks.

Ari Nowacek (EVP and Head of Commercial)

Yeah. Thanks, Charles. New to brand at the moment accounts for roughly 25%-30% of weekly prescription. You know, that's a healthy number at the moment. We expect new to brand to continue to grow, but TRX obviously should outpace just based on the existing patient base and the refill rates, which at this point, we feel very comfortable with. We're seeing good adherence and persistency generally. So hopefully that answered the question. Let me know if there are any specific follow-ups.

Charles Duncan (Managing Director)

Yeah, just a little more color on persistency. I know it's probably too early, but how do you feel about that so far with Auvelity?

Ari Nowacek (EVP and Head of Commercial)

Yeah, I feel really good. In fact, we recently were engaged with a group of KOLs to receive feedback, and this is anecdotal. You know, we don't have specific claim data to prove this out, but they're seeing adherence as, you know, roughly twice what they have seen historically with SSRIs, which bodes very well for the brand. Just showing that, you know, the impact of the clinical profile is meaningful for patients, and they're sticking with it longer than other antidepressants from the past.

Charles Duncan (Managing Director)

Okay. And then in terms of development, perhaps, for you, Ari, can you provide us any information on the % responder rate that you anticipate out of the first part of the ACCORD-2 study? And then a sense of, how you feel brexpiprazole has changed... that unmet need, would you anticipate AXS-05 to become frontline, or would it, I guess, sequence after Brex, brexpiprazole use in those patients? Thanks.

Herriot Tabuteau (CEO)

So thanks for the question. With regard to the responder rate in ACCORD-2, I don't want to commit to speaking in terms of the exact responder rate, but it is exactly what we modeled or what we included as the inclusion criterion in ACCORD-1. So the studies are very similarly designed and as a reminder, the ACCORD-1 trial was able to, you know, very effectively detect a signal. In terms of brexpiprazole and unmet need, we don't view that brexpiprazole has changed the need for a safe and effective, you know, long-term treatment for Alzheimer's disease agitation. So as a reminder, patients will be treated off-label necessarily with atypical antipsychotics. Brexpiprazole does fall into that class.

So we don't view the opportunity for AXS-05 as changing materially based upon that approval. Then in terms of the frontline usage, assuming that we continue to generate data that replicates what we saw in ADVANCE-1 and also in ACCORD-1, we would still expect that AXS-05 could be a frontline treatment and will be a frontline treatment for Alzheimer's disease agitation.

Charles Duncan (Managing Director)

Makes sense. Thanks for taking my questions.

Operator (participant)

Our next question comes from Leonid Timashev with RBC Capital Markets. Please proceed with your question.

Leonid Timashev (Analyst)

Hey, guys. Congrats on a quarter, good quarter, and, thanks for taking my question. Can you just talk about the price volume impact you'd expect from this latest GPO add? And should we expect some acceleration in scripts with an impact to gross to net, in the near term, or would it be more incremental and gradual change? And then maybe just related to that, with two out of the three, major GPOs in hand, can you talk about maybe the progress with the third that you've made? Thanks.

Ari Nowacek (EVP and Head of Commercial)

Yes, thanks, Leonid. This is Ari. So regarding price volume trade-off, it's a little premature to talk about impact on gross to net after this particular agreement. And obviously, part of the effort right now is to ensure that we're effectively pulling through the contract terms with the PBMs that are underneath the GPO umbrella. But we do expect there to be volume growth once we are able to expand coverage, and we'll provide updates on the impact of the gross to net, you know, when appropriate. Regarding your question around the third GPO, what I'd say is, you know, we're having very fruitful discussions with all of the major payers and PBMs, including the GPOs. And you know, these are complicated negotiations.

Obviously, it's important for us not only to expand coverage but to also be mindful of profitability over the long term, because we have a growing portfolio that we need to plan for. So, no specifics on the details of the negotiation, but we feel very good about the nature of the dialogue and look forward to future updates.

Leonid Timashev (Analyst)

Thanks.

Operator (participant)

Our next question comes from Ashwani Verma with UBS. Please proceed with your question.

Ashwani Verma (Analyst)

Hi, thanks. Thanks for taking our questions. Congrats on the progress. So I have two. One is just on this last comment you had about the GPO win. Can you maybe elaborate, like, what percentage commercial lives are covered through this GPO? You have 48% coverage prior to this, I believe. And then second, regarding this new study for AD agitation, can you remind us, like, is that something that you need for a regulatory package? Or do you think that the ADVANCE-2 study would be sufficient? Like, why do this study now versus you already have another study going on, and you had a successful randomized withdrawal study earlier. So just wanted to get your thoughts on that. Thanks.

Herriot Tabuteau (CEO)

Sure, thanks for the question. So with the two questions there, I'll take the last one, and then and I'll turn it over to Ari to answer the first question. So, with regards to the trial, no, we do not need it for a regulatory submission. This is an opportunity for us to increase the robustness of the program while also not affecting at all the timing of an IND submission. So, it just makes sense. You know, we want to have the most robust package, the strongest package going into an IND review. And, such an important indication, it's always helpful to generate additional data, which may also, you know, which may also, not just in terms of a regulatory submission, but also in terms of future publication, be useful from a commercial perspective.

So, you know, we think it is the right thing to do. It's very efficient. It allows us to leverage a large number of patients, who experienced a stable responses in the current approved indication for the trial.

Ari Nowacek (EVP and Head of Commercial)

... Yeah, Ash, this is Ari. Your question around percent of lives with new GPO. Obviously, as you know, the GPOs represent a pool of PBMs. And so, because each of the PBMs has a different number of lives covered, and has the ability to make their own coverage decisions, I can't give you a specific number of the incremental percentage of lives covered, but it is meaningfully above the 48% that we have publicly stated today. And so part of our focus, you know, moving forward is to ensure that the majority of the PBMs and the new phase GPOs are accessing the rates that we've agreed to. So it is a meaningful percentage increase if we were successful with all of the PBMs underneath the umbrella.

Operator (participant)

Our next question comes from Ram Selvaraju with H.C. Wainwright. Please proceed with your question.

Ram Selvaraju (Managing Director, Healthcare Equity Research)

Thanks so much for taking my questions. Just very quickly, on the commercial front, I was wondering if there are specific factors that you expect to impact discussions with the third of the three largest GPOs that you are currently looking to secure, contracting for Auvelity with? And if so, what those factors might be. And then on the development side, I was wondering, Ari, maybe if you could comment on the profile of AXS-12 relative to the existing approved marketed agents, and whether you believe the impact on cataplexy is likely to be the most significant selling point, and if you anticipate that the impact on sleepiness is going to be sufficient for AXS-12 to be positioned commercially in a competitive way in this indication. Thanks.

Ari Nowacek (EVP and Head of Commercial)

Sure. I'll start with the first question. So factors that impact negotiations, generally speaking, are the demand growth that we're driving in the marketplace. And in fact, all of the recent access discussions we've had really focus on how quickly the brand is growing. And so, you know, the best way to secure access is to show volume growth in the absence of formal coverage. I think it's important to note that, you know, as a rule, while we negotiate for coverage with major plans and PBMs, one of the areas of focus has been to optimize our patient savings and reimbursement support services to support continuing demand growth within the existing access paradigm.

Our ability to drive growth is the primary factor in driving interest with GPOs and major plans and PBMs. So we're really proud of the growth that we've seen to start off the year. I mentioned on my opening comments that we've seen about a 30% increase in weekly new patient starts, March compared to December, and that's with the existing access we have. So that only strengthens our ability to negotiate and ultimately have meaningful discussions with the insurance companies.

Ram Selvaraju (Managing Director, Healthcare Equity Research)

Great. Have you started doing DTC promotion of Auvelity, and if so, you know, to what extent?

Ari Nowacek (EVP and Head of Commercial)

Well, we have DTC largely in the digital space at the moment. We do not currently have a TV or video ad that's running, but that is something that is under consideration at the moment, and, you know, we'll share updates when appropriate.

Ram Selvaraju (Managing Director, Healthcare Equity Research)

Great. Thanks.

Herriot Tabuteau (CEO)

So, Ram, with regards to the question on AXS-12 and the profile. So what we saw in the phase 3 trial, which was a replication of what we saw in the concert study, was a pretty important significant impact on cataplexy. So not only was there a large percent reduction in cataplexy, but we looked at remission of cataplexy, which is total elimination. The results were very stark. So a third of the patients had 100% reduction in cataplexy attacks versus less than 10% of patients in the placebo group. And we also did see an impact on excessive daytime sleepiness severity as well as cognition. So we like the profile, and the profile as it relates to agents that are currently on the market is incredibly favorable.

We know that of the agents that are on the market, not all patients, in fact, a minority of patients, actually tolerate them, so there is a significant unmet need. We did conduct also a very large patient survey of MC one patients in conjunction with Narcolepsy Network. And what that shows is that even on current treatments, 77% of patients continue to experience cataplexy. As it relates to the question around whether around the EDS data that we generated, if that would be enough for clinicians and patients to think about adopting the product, what we saw in the study was a clear impact on excessive daytime sleepiness. And we also saw a clear impact on overall narcolepsy severity.

So AXS-12 reduced that excessive daytime sleepiness severity, but also, improved overall narcolepsy severity as well as quality of life. So the way that we think about it is, should this product be made available to clinicians and to patients, that profile will be very apparent, to, to the patient and to clinicians when it's treated based on the patient-reported outcomes as well as the clinician global impression, outcomes. So we really like the profile, and, we think it will be important treatment for patients.

Ram Selvaraju (Managing Director, Healthcare Equity Research)

Thank you very much.

Operator (participant)

Our next question comes from Marc Goodman with Leerink. Please proceed with your question.

Marc Goodman (Senior Managing Director)

Good morning. Nick, can you talk about was there any inventory for Auvelity in the quarter, anything unusual that that may have helped sales? And second, can you talk about gross to net, how you're thinking about the rest of the year? And with these contracts that are now being put in place, you know, how should we be thinking about over the next couple of years? And then Ari, can you just talk about AD agitation for one second? Obviously, you know, last quarter, you delay, by, we're not exactly sure, but into the second half, the completion of Advance 2. Maybe you can just give us a little more color there, like are we, are we now back on track?

Is this gonna be something that's gonna happen early in the second half of the year, or is this late in the second half of the year? And, and just to confirm that this new study that you're talking about here, this is just patients who've already gone through that open label, so it's not really, competing against it at all, right? Thanks.

Nick Pizzie (CFO)

Hey, Marc, it's Nick. So for inventory, inventory remains in channel at two weeks. So nothing has changed specifically around inventory for Auvelity nor Sunosi remains continuing at two weeks. And then the Auvelity GTN discount for Q1 was in the low- to mid-50s, and Sunosi GTN discount was in the mid-50s for the quarter. As you know, Q1 typically does have a seasonality, a negative seasonality effect on GTN, which we both saw in the Auvelity and Sunosi versus the prior quarter. For Auvelity, GTN did fluctuate in Q1, and ended the quarter with March being in the mid-50s, and right now we have no reason to expect it to vary significantly from that level moving forward.

Marc Goodman (Senior Managing Director)

Okay, great.

Herriot Tabuteau (CEO)

Marc, in relation to the questions around Alzheimer's disease agitation. So starting with Advance 2, the guidance is the second half of this year. We're very comfortable. We remain very comfortable with that guidance based on enrollment trend. So what we're seeing is very positive with regards to how that study is proceeding. And then, as it relates to Cohort 2, it is not competing with Advance 2. So you are correct. So we have a large number of patients who are able to be enrolled fortunately, who are experiencing stable responses. So that allows us very efficiently to enroll Cohort 2. So we do expect for enrollment in Cohort 2 to complete mid-year.

You know, the reason for the confidence around that is that the study is very well along in terms of enrollment.

Marc Goodman (Senior Managing Director)

Just to understand for ADVANCE-2, enrollment really picked up over the past three months, and that's why you're confident?

Herriot Tabuteau (CEO)

So we're confident based on where enrollment was and has been. Enrollment in ADVANCE-2 also is very well along, and it continues to enroll at a predictable pace.

Marc Goodman (Senior Managing Director)

Okay, thanks.

Operator (participant)

Our next question comes from David Amsellem with Piper Sandler. Please proceed with your question.

David Amsellem (Managing Director and Senior Research Analyst)

I have a couple of questions on the pipeline. First, for reboxetine, in narcolepsy, can you just remind us of the path forward? In other words, are you expecting to file after your ... You completed the, the extension, or are there any other gating items to an NDA filing? So can you talk about that and your timeline to filing on reboxetine in narcolepsy slash cataplexy. Then, solriamfetol, can you talk to your pediatric ADHD study plan? I believe that's a gating item to your filing in ADHD, so it would be helpful to talk to that. And then lastly, esreboxetine and fibromyalgia.

How big of a commercial priority is that, and what's the extent to which you're going to need to expand the commercial organization to support that product commercially? Thank you.

Herriot Tabuteau (CEO)

Thank you for those questions. So, I'll take the first two and then for Solriamfetol, and then I'll let Ari comment on esreboxetine. So in terms of the timing for the ADHD filing for AXS-12, so the gating factor is completion of the stability file, which we expect to complete in the second half of this year. And then, it'll take us then some time to put together the NDA filing, but that is the gating factor. So once that study is completed, we will then be able to file the NDA. As it relates to Solriamfetol and the pediatric ADHD study plan, you are correct that that is a trial which will be part of the initial NDA package.

We've been working on that, as you can imagine, in terms of speaking with the FDA to get that in place. We've not yet provided the precise guidance, but it is a study that we will be targeting to start this year. With regards to Etodolac.

Ari Nowacek (EVP and Head of Commercial)

Yeah, thanks for the question. I think for AXS-14 and fibromyalgia, we do view this as a meaningful commercial opportunity. There are three approved agents, but there's a lot of room for improvement in terms of overall clinical profile for patients, and we feel very optimistic about the profile AXS-14 offers for patients. As it relates to, you know, how it will impact the sort of commercial footprint, you know, part of what we're analyzing this year is how to effectively size and structure our sales force to accommodate a growing portfolio of products. Although fibromyalgia is not, you know, a psychiatric product, there is a lot of overlapping comorbidity with major depressive disorder that will influence some of our thinking.

And so it's a little too early to say, you know, how many additional reps we would wanna build into the plan or how we would structure it, but we do think that there's a way to promote AXS-14 efficiently while also putting plenty of attention on the other approved products on the market.

David Amsellem (Managing Director and Senior Research Analyst)

That's helpful. Thank you.

Operator (participant)

Our next question comes from Yatin Suneja with Guggenheim Partners. Please proceed with your question.

Yatin Suneja (Senior Managing Director and Biotechnology Analyst)

Hey, guys. Thank you for taking my question. I have two quick ones. One is a clarification one. With regard to the ACCORD-2 study, so that's a new study, and this is a full study within the ADA umbrella. Is that a requirement from the FDA that you have to do two randomized withdrawal study? And then will the NDA package be contingent upon completion of that study or the outcome of that study? So that's one. And then with regard to Auvelity, I mean, very nice quarter, so congrats on that. Any thoughts on thinking about providing guidance for the product, maybe on a quarterly or on a yearly basis? Thank you.

Ari Nowacek (EVP and Head of Commercial)

Yeah, yeah. So-

Nick Pizzie (CFO)

Sure. Hey, Yatin. Thanks for the question. It's Nick. It's just too early in Axsome and Auvelity's life cycle to provide sales guidance, given the fluid nature of some of the market dynamics and the unpredictability of external factors that could have different impacts. We have shared that we believe peak sales for Auvelity and Sunosi alone are in the $1-$3 billion range, and Sunosi, $300-$500 million, for its current indications.

Yatin Suneja (Senior Managing Director and Biotechnology Analyst)

Okay.

Herriot Tabuteau (CEO)

Yatin, with regards to ACCORD-2, this is not an FDA requirement. However, it does increase the robustness of the package, and it is a pivotal trial, so we like that. We like having four different studies. So basically, if you think about it, ADVANCE-1 and ADVANCE-2 are two parallel group studies, and ACCORD-1 and ACCORD-2 are two randomized withdrawal studies. So a very nice source of evidence generation with those four studies. And then with regards to the filings and contingent on upon completion of that study, so it's not required. It's not really contingent.

However, you know, we do think that based upon where we are with enrollment of that study, and we expect the study to be fully enrolled mid-year, and also the timing of the relapses in the ACCORD 1 trial, which was positive, that there is a potential for that study to be that around year-end. That's not formal guidance, and formal guidance usually depends upon the number of relapses and timing of relapses, but just to give you a sense of how one might think about it. So, we're really happy with the way that we've been able to efficiently increase the robustness of the program for a very important product.

Operator (participant)

Our next question comes from Jason Gerberry with Bank of America. Please proceed with your question.

Jason Gerberry (Managing Director and Equity Research Analyst)

Hey, guys. Thanks for taking my question. So just on ACCORD-2, so it sounds like the motivation with the study is that, you know, kind of like, think about it as a marketing study. And along those lines, is there an opportunity for you to pool ACCORD-1 and ACCORD-2 such that... I don't know if the data has a better chance of getting into the label, given that ACCORD-1 was a really small trial. And then, you guys did mention the cyberattack in 1Q. So, I know some of your peers had kind of indicated it wasn't really a material impact to the numbers. So can you quantify to what extent the cyberattack did affect Auvelity revenues in 1Q? Thanks.

Herriot Tabuteau (CEO)

So with regards to ACCORD-2, just to be clear, it can be used for marketing, obviously, but it is a registration trial. So, you know, we like that. So it does provide a very objective source of evidence. And it relates to the pooling with ACCORD-1, the two studies, even if they're similarly designed, could definitely be combined, and that's typically something that is done in new packages.

Ari Nowacek (EVP and Head of Commercial)

Yeah, and regarding the Change Healthcare cyberattack, the impact for Auvelity was really focused on two weeks at the end of February, beginning of March. Basically, what we saw was, you know, roughly a 30%-40% impact on weekly prescriptions for those couple of weeks. During that time, we put in a number of technology optimizations and patient savings optimizations. We saw a very quick bounce back in early to mid-March for our demand trend, and it's been stable since then, stable to growing, since then. So it's largely behind us at this point. We don't expect any continued disruption.

And, you know, for some brands, it was more impactful just related to time to market, you know, whether patient savings cards were tied to the Change Healthcare switch, things of that nature. So that's why it impacted us, but it was transient in nature. We feel really good about the solutions we put into place, and we've seen really nice growth since.

Jason Gerberry (Managing Director and Equity Research Analyst)

Thank you.

Operator (participant)

Our next question comes from Joon Lee with Truist Securities. Please proceed with your question.

Joon Lee (Managing Director and Senior Biotech Analyst)

... Thanks so much. Question. Regarding ACCORD-2, what was the rationale behind designing it as a randomized controlled trial against the standard trial comparison trial? And are the endpoints in ACCORD-2 identical to that used in ACCORD-1? Thank you so much.

Ari Nowacek (EVP and Head of Commercial)

So thanks, Joon. You were somewhat muffled, so I'll try and answer the question the way that I interpreted it, but not necessarily what you said. But I think the question was around Accord 2 and what was the rationale for the design versus other designs? So the rationale was we wanted to take advantage already of the fact that we had a study which was treating patients in an open-label fashion and therefore would allow assessment of stable response. So it made a lot of sense. So since that our open-label safety extension trial is essentially the same way that all randomized controlled studies do it. So that was the rationale there. And in terms of the endpoint, as compared to Accord 1, the endpoint is identical.

This is a way for us to be able to take the learnings from ACCORD-1 and apply them to ACCORD-2 to generate additional data.

Joon Lee (Managing Director and Senior Biotech Analyst)

Thank you.

Operator (participant)

Our next question comes from Joel Beatty with Baird. Please proceed with your question.

Joel Beatty (Biotechnology Equity Research Analyst)

Hi, thanks for taking the questions. The first one is on Auvelity. Can you provide the breakdown between usage and earlier line and later line therapy? And with the second-largest purchasing contract, could the usage of earlier line therapy be impacted at all?

Ari Nowacek (EVP and Head of Commercial)

Yeah. Hey, this is Ari. Thanks for the question. We have seen a really nice increase since last quarter in line of therapy. The increase is, we saw, you know, roughly 5% increase in first or second line use. So, at this point, we're around 50% of Auvelity prescriptions are first or second line, which is, you know, a very healthy trend, and we expect that to continue. Your question around the GPO contract and the impact on line of therapy, generally speaking, when we negotiate with plans and PBMs, we are negotiating for first or second line access for patients. And so we would expect, if we're successful in pulling through that, those contract terms, that that would further increase, you know, the earlier usage of Auvelity in patients.

Joel Beatty (Biotechnology Equity Research Analyst)

Thanks. Last question is, can you provide any kind of context on how this funding trajectory is looking going forward?

Ari Nowacek (EVP and Head of Commercial)

I'm sorry, you were hard to hear. Do you mind repeating the question?

Joel Beatty (Biotechnology Equity Research Analyst)

Sure. How does this, funding trajectory look going forward, just funding overall for our R&D and SG&A and so on?

Nick Pizzie (CFO)

Got it. Thanks, thank you for your question. As for R&D, our expense for the quarter was $37 million, which ticked up slightly from the previous quarter. We expect R&D spend to continue to increase gradually as the two, celariax and pulse phase 3 trials commenced during the quarter, with the third starting in Q2, in Chip work. These will be partially offset by the completion of the SYMPHONY trial for AXS-12. And as a reminder, in Q2, we do plan to submit the NDA for fibromyalgia, so we will have a one-time charge for the NDA filing fee. As for SG&A, total expense for the quarter was $99 million, as I mentioned in my opening remarks. That was higher than the previous quarter than anticipated as it related to the sales force expansion.

We would anticipate SG&A expense to be in this range in future quarters.

Joel Beatty (Biotechnology Equity Research Analyst)

Thank you.

Operator (participant)

Our next question comes from David with Sidney. Please proceed with your question.

Speaker 19

Hi, good morning, and thanks for taking my question. Congrats on the quarter. I want to ask about the impact of the GPO negotiations in terms of timing on, you know, any increases in the number of commercial covered lives. Just, I guess, what could the cadence in covered lives that you pick up look like? And can we look towards next quarter as, you know, potentially seeing a meaningful step up in the number of covered lives? Thanks.

Ari Nowacek (EVP and Head of Commercial)

... Thanks for the question, David. So we expect coverage to increase, but it is difficult to predict the exact timing. The way to think about GPOs are effectively gatekeepers for PBMs, which is why the first step towards securing access is agreeing on contract terms, which include the rebates and immunization management parameters. So the agreement we have today enables the PBMs under that umbrella to now access the contracted rates for their members. I can't provide a specific percentage increase in covered lives from the 48% we have today, but I will say that, depending on how many of the PBMs that are underneath that umbrella access the rate, it is a meaningful increase over and above the 48%. The timing is just, it's too difficult to provide.

Your question about next quarter, obviously, our intent is to try to improve it as quickly as possible, and we'll provide updates at the appropriate time.

Operator (participant)

Our next question comes from Graig Suvannavejh with Mizuho. Please proceed with your question.

Speaker 20

Hi, this is Avantica for Greg. I just had a question about AXS-05. Have you thought more about the branding for AXS-05 and AD agitation, and if you keep it under the Auvelity brand? Thanks, and congrats on the quarter.

Ari Nowacek (EVP and Head of Commercial)

Yeah, thanks, thanks for the question. So I—whenever you have a new indication, and especially one which is different, as it is in the case of AXS-05, things like that versus major depressive disorder, that is well with the consideration, and it's one that requires a lot of good thought. And it's not just something that we just answer on the fly. So which would require us to really think about it and do some quantitative work. So stay tuned and confirming that we would not obviously communicate or announce ahead of time, but it's something that we're working on. Did you add to that?

Herriot Tabuteau (CEO)

No, I think you're spot on, and I think the reality is that there are advantages and disadvantages to either maintaining the same name or having an alternative brand name, and we're going through the work right now, in anticipation of a filing down the road.

Speaker 20

Great. Thank you.

Operator (participant)

Our next question comes from Vikram Purohit with Morgan Stanley. Please proceed with your question.

Vikram Purohit (Executive Director)

Hi, good morning. Thanks for taking our questions. We have two, one on Auvelity, one on the pipeline. So for Auvelity, could you talk a bit more about how you expect the salesforce expansion that you completed recently to help kind of inflect scripts and inflect sales throughout the rest of the year? And whether you'd expect there to be kind of a visible kind of acute lift in either of those metrics over the next couple of quarters? And then secondly, for solriamfetol and ADHD, can you confirm, is this phase 3 readout expected in the second half of the year? Is this going to be the study based on which you can submit potentially a filing for the indication?

And then also, if you could just kind of frame out for us, what you'll be reporting and what you would think, constitutes a successful readout here, that'd be helpful? Thank you.

Ari Nowacek (EVP and Head of Commercial)

Sure. Yeah, I'll start with the Auvelity question. So, sales force expansion, we are seeing an impact certainly on activity levels and effort with customers. We're seeing, you know, roughly, a 40% increase in weekly calls to customers. We are engaging with a broader group of providers that includes a primary care audience. And we are seeing a meaningful increase in new prescriptions and total prescriptions from primary care, which is sort of commensurate with the additional focus we've been able to provide with the expanded sales team. I would say that we're in the early phases of seeing the impact from a demand perspective. Referenced on the opening comments that we've seen a 30% increase in weekly new patient starts.

That is typically the first indicator that demand growth is reaching an inflection. But it's still early days in many ways. And we expect that net growth to continue over time. So we feel really optimistic about the impact the sales force expansion has thus far and expect that to continue to build over the course of the year.

Vikram Purohit (Executive Director)

Great. And with regards to Solriamfetol and the current study, that phase 3 trial is a registration trial, so this is the study that would enable a new filing, along with a study in pediatric patients. So we do need to include that data and efficacy data from pediatric patients. That's required for any kind of ADHD filing. So we are looking forward to the results of the phase 3 trial in the second half of this year. So we're on track for that. As it relates to what we're looking for, well, I think the first thing that we're looking for is to demonstrate efficacy in the first large multicenter randomized parallel group study. So that's what we're, we're looking for. The result of that will inform the profile of the product. There has been one prior study which-...

Herriot Tabuteau (CEO)

We have a call in ADHD, which Sharon sponsored. That was an executive initiative trial. That was a single-center study. This will be, the FOCUS study will be the first multicenter trial.

Operator (participant)

Our next question comes from Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.

Matt Kaplan (Managing Director and Head of Healthcare Research)

Hey, good morning, guys, and, congrats on the quarterly results. Just a quick follow-up on the ADHD program for solriamfetol. Will you, I guess, wait for the readout of the adult study prior to starting the pediatrics study in ADHD?

Herriot Tabuteau (CEO)

No, we will not. Our goal is to start the pediatric study as soon as practical.

Matt Kaplan (Managing Director and Head of Healthcare Research)

Great. Thanks.

Operator (participant)

We have time for questions from two more analysts. Our next question comes from Myles Minter with William Blair.

Myles Minter (Biotechnology Equity Research Analyst)

Hey, guys. Thanks for taking the questions. Just on the Alzheimer's disease education program, you're enrolling from the open label extension of ADVANCE-2 into this new ACCORD-2 study. So does that really imply that you've already got all of the long-term safety data that is required for a potential AXS-05 filing for that indication? And then the second one is about the messaging that ACCORD-2 could be a pivotal study if it is required. Why is that the case when I believe ACCORD-1 went through some protocol amendments and was obviously concluded early? And I think the messaging was that that may have been pivotal when it first started, and it turns out it wasn't. So I guess, what has changed there to say that ACCORD-2 would be pivotal and ACCORD-1 wasn't? Thanks.

Herriot Tabuteau (CEO)

Thanks, thanks for the question. With regards to, the open label extension study, so we continue to, to enroll the open label safety extension trial. As a reminder, that requires, or what we're trying to do with the guidelines, which are 300 patients treated for six months and 100 patients treated for one year, and we're well on track to accomplish those goals. So of course, we would not affect that. And then, also the, the patients, who are completing ACCORD 2 are also able to then go on and continue to be dosed. So we're very comfortable with regards to meeting the necessary number of patients. And it relates to, ACCORD 2, the pivotal study, and also comparing that to ACCORD 1.

So what's nice about ACCORD-2 is that we did ACCORD-1, and so all of the learnings in terms of our content around the endpoint, which would be necessary in a study like this, we have. And so we were able to design ACCORD-2 very prospectively and we have also received feedback from the FDA that this could be a registration trial based on the design. So I think, you know, that is the fact that that ACCORD-2, we are designing and we have designed it with the benefit of the knowledge from ACCORD-1, which is an asset in this case.

Myles Minter (Biotechnology Equity Research Analyst)

Thanks for the call.

Operator (participant)

Our next question comes from Troy Langford with TD Cowen. Please proceed with your question.

Troy Langford (Biotech Equity Research VP)

Hi, congrats on the progress this quarter, and thanks for taking our question. On AXS-14, how confident do you feel that the FDA has all it would need from a, from a clinical efficacy perspective to approve the application? And then on to Sunosi, can you just provide any additional color on the powering assumption to the phase 3 trial in MDD?

Herriot Tabuteau (CEO)

Sure. Hey, I'll take 14 with Mark. So, we're targeting this quarter here. You know, in terms of content, that's essentially complete. So, you know, those things are being finalized and really just building out the submissions. You know, we're going to do that. We're going to take the time to get that as robust as possible, but the work is substantially complete. As it relates to the powering for Solriamfetol in MDD, we powered that study similarly to the way that we powered our other studies in major depressive disorder. So, and, you know, we have quite a bit of experience there with the development program. So, think about the powering as being similar.

I think, you know, in general, when these studies, the effect size is what you'd expect with these drugs, is very well laid out, and there's a lot of precedence, so that's how you would power the study. To summarize, it's 90% power to detect an effect size, which is similar to the effect size which, we detected in the development program.

Troy Langford (Biotech Equity Research VP)

Great. Thanks for the color.

Operator (participant)

Since there are no more questions, I will now turn the call back over to Axsome's CEO for concluding remarks.

Herriot Tabuteau (CEO)

Well, thank you for taking the time to join us for today's quarterly update. The first quarter of 2024 marked strong progress for Axsome. We look to continue our focus on commercial and pipeline execution throughout the balance of the year, with the goal of delivering innovation and value to patients, healthcare professionals, and investors alike. Thank you, and have a great rest of the day.

Operator (participant)

This concludes today's conference. Thank you for your participation. You may disconnect your lines at this time.