Axsome Therapeutics, Inc.

Good morning, and welcome to the Axum 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 Oppen, Director of Corporate Communications at Axome Therapeutics. Please go ahead.

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 axome.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, amongst 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 synopsis, ability, 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. You 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. Ariel Tabuteau, Chief Executive Officer, Nick Pizzi, Chief Financial Officer, Mark Jacobson, Chief Operating Officer, and Ari Maisel, Executive Vice President and Head of Commercial. Ariel will provide an overview of the company and progress made in the first quarter of 2024, as well as key upcoming milestones. Following Ariel, 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. And with that, I will turn the call over to Ariel.

Thank you, Darren. Good morning, everyone, and thank you for joining Axon Therapeutics' first quarter 2024 financial results and business update conference call. The first quarter of 2024 was marked by strong financial performance for our on-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 in the call. We also significantly advanced our innovative neuroscience pipeline in the quarter, including announcing positive top-line results for AXS-12 and narcolepsy, advancing AXS-07 and AXS-14 towards NDA submissions, initiating pivotal trials and new indications with sorianfetol, and advancing and expanding our Alzheimer's disease agitation program for AXS05. 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 NDA stage products, AXS07 for the acute treatment of migraine is on track for an NDA resubmission this quarter. Additionally, we are conducting the eMERGE study, a multi-center phase three single group trial evaluating the efficacy and safety of AXS07 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 AXS14, which we are developing for the treatment of fibromyalgia, pre-submission activities for the NDA for this product are nearing completion. continue to target submission later this quarter. In March, we announced that the Phase III symphony trial of AXS-12 and 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. of 2024. We are excited about the potential of AXS-12 to provide a differentiated treatment option to patients and HCPs for this debilitating condition. Moving on to the AXS-05, we continue to anticipate completion of the Phase III Advanced II trial in the treatment of Alzheimer's disease agitation in the second half of 2024. Today, we announced that we launched the ACCORD II study a double-blind, placebo-controlled randomized withdrawal trial to evaluate the efficacy and safety of AXS05 in the treatment of Alzheimer's disease agitation. This study is similar in design to the completed positive ACCORD1 trial. With ACCORD2, the clinical development program will now include four controlled efficacy trials. Importantly, ACCORD2 further increases the robustness of our clinical program in Alzheimer's disease agitation without impacting our overall development timeline. Enrollment in Accord 2 is very far along, and we expect enrollment completion around mid-year. With respect to Sol-reampetol, our dopamine and norepinephrine reuptake inhibitor and colon agonist, in addition to continued commercial performance, we launched the Phase 3 paradigm trial in major depressive disorder and the Phase 3 engaged 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 three clinical program in chip work disorder this quarter. Solvranfetol is also being evaluated in the FOCUS phase three 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 body candidate has the potential to transform the treatment landscape for 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 of our financial performance.

Nick? Thank you, Ariel, and good morning. Today, I will 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 outlicensing of Synosi in certain ex-U.S. territories. Avelity net product sales were $53.4 million for the first quarter of 2024, representing year-over-year growth of 240%. Avelity net product sales for the comparable period were $15.7 million. Senosi 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 Senosi sales in outlicensed territories. Senosi 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 CINOSI 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 SORI-AMPHITOL paradigm trial for major depressive disorder, the SORI-AMPHITOL ENGAGE trial for the binge eating disorder, the advancement of the SORI-AMPHITOL FOCUS trial for ADHD, the ongoing trials of AXS05 and AXS12, manufacturing costs associated with the anticipated NDAs for AXS07 and AXS14, post-marketing commitments for both Abeldy and Sinosi, 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 Abelody and Senosi, 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 Synosy out-licensing. Q1 typically has a negative seasonality effect on GTN, which we saw in both Avelity and Synosy versus the prior quarter. Avelity GTN discount for Q1 was in the low to mid-50s, and Synosy 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 cashflow positivity based on the current operating plan. I would now like to turn the call over to Ari, who will provide a commercial update.

Thank you, Nick. Axum delivered solid brand performance in the first quarter of 2024. Ovality 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 Ovality in the quarter, bringing the total number of unique patients treated with Ovality 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 ability 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 cyber attack. Payer coverage was stable in Q1, as availability 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 availability, 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 availability based on the contracted terms. With this agreement, Axome is now contracted with two of the three largest GPOs for potential coverage of Avelity. We are very pleased with the strong commercial foundation we have created to support Avelity 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 mobility as a go-to treatment option for adults with major depressive disorder. Transitioning now to synopses. 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 Sanosi treatment during the quarter, bringing the total number of unique patients treated with Synose to approximately 68,000 since launch. More than 400 new writers were activated in Q1, resulting in a total cumulative prescriber base of more than 12,600 since launch. Payer coverage for Synose in Q1 remained 83% of lives covered across channels. In closing, Q1 was a very positive start to 2024 for both Obelity and Synose. with leading indicators such as trends with new patient starts and newly activated prescribers, reinforcing our confidence that Axiom 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 Axiom'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.

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

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star 2 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 re-enter the queue by pressing star 1. 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.

Hey, good morning, Ariel 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. Can you give us a sense of new-to-brand versus refill rates for availability? Thanks.

Yeah, thanks, Charles. New to Brand at the moment accounts for roughly 25% to 30% of weekly prescriptions. 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 answers the question. Let me know if there are any specific follow-ups.

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

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

Okay. And then in terms of development, perhaps for you, Ario, can you provide us any information on the percent 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 AXS05 to become frontline, or would it, I guess, would it sequence after Brex, Brexpiprazole use in those patients?

Thanks. Thanks for the question. With regards to the responder rate in a core tube, I don't want to misspeak in terms of the exact responder rate, but it is exactly what we modeled or what we included at the inclusion criterion in ACCORD-1. So the studies are very similarly designed, and as a reminder, the ACCORD-1 trial was able to very effectively detect the signal. In terms of brexpiprozole, And on that need, we don't view that brextrapazole has changed the need for a safe and effective long-term treatment for Alzheimer's disease agitation. So as a reminder, patients who are being treated off-label necessarily with antipsychotics, brextrapazole does fall into that class. And so we don't view the opportunity for AXS05 as changing materially based upon that approval. And then in terms of frontline usage, assuming that we continue to generate data that replicates what we saw in Advance 1 and also in Accord 1, we would fully expect that AXS05 could be a frontline treatment and would be a frontline treatment for Alzheimer's disease agitation.

Makes sense. Thanks for taking the questions.

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

Hey, guys. We're right on a quarter, a good quarter, and thanks for taking my question. Can you just talk about the price volume impact you'd expect from this latest GPO ad? 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, 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.

Yeah, thanks, Wayne. This is Ari. So, regarding price volume trade-off, it's a little premature to talk about impact on gross to net for 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 the impact of the gross to net when appropriate. Regarding your question around the third GPO, what I'd say is we're having very fruitful discussions with all of the major payers and PBMs, including the GPOs. And these are complicated negotiations. Obviously, it's important for us not only to expand coverage but 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.

Thanks.

Our next question comes from Ash Burma with UBS. Please proceed with your question.

Hi, thanks for taking your questions. Congrats on the progress. So I had to, just on this last comment that 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.

Sure, thanks for the question. Two questions there. I'll take the last one, and then I'll turn it over to Ari to answer the first question. So with regards to the accord to 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 NDE submission. So it just makes sense. We want to have the most robust package, the strongest package going into an NDE review, and this is 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 publications, be useful from a commercial perspective. So we think it was the right thing to do. It's very efficient. It allowed us to leverage a large number of patients who are experiencing stable responses in the current open-label safety extension trial.

Yeah, Ashley, 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 underneath those 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.

Our next question comes from Ram Salvatore with HC Wainwright. Please proceed with your question.

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 availability with, and if so, what those factors might be. And then on the development side, I was wondering, Ariel, 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 syndication space.

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 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 of PBMs, one of the areas of focus has been to optimize our patient savings and reimbursement support services to support continued demand growth within the existing access paradigm. And our ability to drive growth is the primary factor in driving interest with GPOs and major plans and PBMs. And 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.

Have you started doing DTC promotion of Auvility, and if so, to what extent?

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 we'll share updates when appropriate.

Great, thanks. So, Ron, with regards to your question on AXS-12 and the profile, so what we saw in the FIFNI trial, which was a replication of what we saw in the CONCERT study, was a pretty significant impact on cataplexy. So not only was there a large percent reduction in cataplexy, but if you 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 excessively transsexual 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. And we did conducted also a very large patient survey of NC1 patients in conjunction with Narcolepsy Network. And what that showed was that even on current treatments, 77% of patients continue to experience cataphylaxis. As it relates to your question 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 Intoxicative Sleepiness. And we also saw a clear impact on overall narcolepsy severity. So AXS-12 reduced Excessive Intoxicative Sleepiness severity, 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 patients 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 this will be an important treatment for patients.

Thank you very much.

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

Good morning. Nick, can you talk about, was there any inventory for availability in the quarter, anything unusual 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 it over the next couple of years? And then, Ariel, 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 two. Maybe you can just give us a little more color there, like are we now back on track? Is this going to be something that's going to happen early in the second half of the year? Is this late in the second half of the year? 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.

Hey, Mark. It's Nick. So for inventory, inventory remains in-channel at two weeks. So nothing has changed specifically around inventory for Velody nor Synosy. Remains continuing at two weeks. And then the Velody GTN discount for Q1 was in the low to mid-50s, and Synosy GTN discount was in the mid-50s for the quarter. As you know, Q1 typically does have a negative seasonality effect on GTN, which we both saw in the VALIDI and CINOSI versus the prior quarter. For VALIDI, 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.

Great. And, Mark, as it relates to the questions around all dynamics of these agitations, So starting with Advance 2, the guidance is second half of this year. We're very comfortable. We remain very comfortable with that guidance based on the trend. So what we're seeing is very positive with regards to how that study is proceeding. And then as it relates to Accord 2, it is not competing with Advance 2. So you are correct. We do have a large number of patients who are in the open-label portion who are experiencing states of responses, so that allows us very efficiently to enroll in Accord 2. So we do expect for enrollment in Accord 2 to complete mid-year, and the reason for the confidence around that is that the study is very far along in terms of enrollment.

And so just understand for Advance 2, enrollment really picked up over the past three months, and that's why you're confident.

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

Okay, thanks.

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

I have a couple of questions on the pipeline. First, for riboxetine in narcolepsy, can you just remind us of the path forward? In other words, are you expecting to file after you've 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 riboxetine and narcolepsy slash cataplexy? Then psori amphetol, can you talk to your pediatric ADHD study plan? I believe that's a gating item to a filing in ADHD, so it would be helpful to talk to that. And then lastly, 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.

Thank you for those questions. So I'll take the first two on the exit, 12 and 12-ampetal, and then I'll already comment on estrobocytin. So in terms of the timing for NDA filing for AXS-12, so the gating factor is completion of the Open Label Safety Extension Trial, 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 salivary epithelial and the pediatric ADHD study plan, you are correct that that is a trial, which means it's part of the initial ID package. And we've been working on that, as you can imagine, in terms of speaking with the FDA to get that in place. And we've not yet provided the precise guidance, but this is a study that we will be targeting to start this year. And with regards to estradiol,

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 how it will impact the sort of commercial footprint, 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 a psychiatric product, there is a lot of overlapping comorbidity with major depressive disorder that will influence some of our thinking. It's a little too early to say how many additional reps we would want to build into the plan or how we would structure it, but we do think that there's a way to promote AXS14 efficiently while also putting plenty of attention on the other approved products on the market.

That's helpful.

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

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 to randomize 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 availability, 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.

Yeah, yeah. Sure.

Hey, Yachtin. Thanks for the question, Nick. It's just too early an axiom in availability of lifecycle 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 availability in MVD alone are in the $1 billion to $3 billion range and Sanosi $300 million to $500 million for its current indications.

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. We like that. We like having four different studies. 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. a very nice source of evidence generation with those four studies. And then with regards to the filing, is it contingent upon completion of that study? Since it's not required, it's not really contingent. However, we do think that based upon where we are with enrollment of that study, so we expect the study to be fully enrolled mid-year, and also timing of the relapses in the ACCORD-1 trial, which was positive, that there is the potential for that study to bleed out around year-end. That's not formal guidance. And formal guidance will be based upon the number of relapses and the 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 this very important product.

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

Hey, guys. Thanks for taking my question. So just on Accord 2, so it sounds like the motivation with the study is that 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 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 cyber attack in 1Q. So I know some of your peers had kind of indicated it wasn't really a material impact number. So can you quantify to what extent the cyber attack did affect ability revenues in 1Q? Thanks.

So with regards to Accord 2, just to be clear, this is – It can be used for marketing, obviously, but it is a registration trial, so we like that. It does provide a very objective source of evidence, and it relates to being able to pull it with a 4-in-1. The two studies, because they're similarly designed, could definitely be combined, and that's typically something that is done in NDA packages.

Yeah, and regarding the Change Healthcare cyber attack, the impact for Abelity was really focused on two weeks at the end of February, beginning of March. Basically what we saw was roughly 30% to 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 and 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 in market, you know, whether patient savings cards were tied to the change healthcare switch, things of that nature. And 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.

Thank you.

Our next question comes from June Lee with Truce Securities. Please proceed with your question.

Thanks for taking our questions. Regarding Accord 2, what was the rationale behind designing it as a randomized control file as opposed to a standard catalog and storage file, which you have been assessing? And are the endpoints in Accord 2 identical to that used in Accord 1? Thank you so much.

Thanks, June. You were somewhat muffled, so I'll try and answer the question the way that I interpreted it, but not necessarily what you said. I think the question was around a Core 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 since our open label safety extension trial is essentially the same way that all randomized referral studies begin. So, that was the rationale there. In terms of the endpoint as compared to Accord 1, the endpoint is identical. So, 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. Thank you.

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

Hi. Thanks for taking the questions. The first one is on availability. Could you provide a breakdown between uses in earlier line and later line therapy? And with the second large purchasing contract, could the uses in earlier line therapy be impacted at all?

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 all ability 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 those contract terms, that that would further increase, you know, the earlier usage of availability in patients.

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

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

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

Got it. Thanks for your question. So 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 Sol Reamphitol Phase 3 trials commence during the quarter with the third starting in Q2 in shift 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 of the quarter was $99 million, as I mentioned in my opening remarks. That was higher than the previous quarter when anticipated as it really related to the Salesforce expansion. We would anticipate SG&A expense to be in this range in future quarters.

Thank you.

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

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? Can we look towards next quarter as, you know, potentially seeing a meaningful step up in the number of covered lives? Thanks.

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 it, 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 utilization management parameters. So the agreement we announced 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 cover lives from the 48% we have today, but I will say that depending on how many of the PBMs underneath that umbrella access the rate, it is a meaningful increase over and above the 48%. The timing is just too difficult to provide, and 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.

Our next question comes from Greg Souveneglia with Mizuho. Please proceed with your question.

Hi, this is for Greg. I just had a question about AXS05. Have you thought more about the branding for AXS05 and AD Agitation, and if you would keep it under the Avelity brand? Thanks, and congrats on the quarter.

Yeah, thanks for the question. So, whenever you have a new indication, and especially one which is different, as it is in the case of SFO5, pulmonary pulmonary disease excitation, versus major tracheic disorder. That is always a consideration, and it's one that requires a lot of good thought, and it's not just something that can just be answered on the fly. So this would require us to really think about it and do some quantitative work. So stay tuned. This is something that we would not obviously communicate or announce ahead of time, but it's something that we're working on. Ari, anything that you would add to that?

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 filing down the road.

Great, thank you. Our next question comes from Dicker with Morgan Stanley. Please proceed with your question.

Hi, good morning. Thanks for taking our questions. We had 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 Sahl, Rian, Patel, and ADHD, can you confirm, is this phase three 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

successful readout here that'd be helpful thank you sure yeah i'll start with the ability question so uh salesforce expansion we we are seeing an impact um certainly on activity levels and effort with customers we're seeing a you know roughly a 40 increase in in weekly calls to customers we are engaging with a broader group of providers that includes a primary care audience And we are seeing that 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 growth to continue over time. So we feel really optimistic about the impact the Salesforce expansion has had thus far and expect that to continue to build over the course of the year. Great.

And with regards to solar amphetol and the current ADHD study, that phase three trial is a registration trial. So, this is the study that would enable an NDE filing along with a study in pediatric patients. So, we do need to include data and efficacy data from pediatric patients that's required for any kind of ADHD MD filing. We're looking forward to the results of the FOCUS III trial in the second half of this year, so we're on track for that. As it relates to what we're looking for, I think the first thing that we're looking for is to demonstrate efficacy in the first large multi-center randomized parallel group study. That's what we're looking for. The results of that will inform the profile of the product. There has been one prior study with psilocybin in ADHD, which we sponsored. That was an investigative-initiated trial. That was a single-center study. So this will be, the focus study will be the first multi-center trial.

Our next question comes from Matt Kaplan with Lindenberg Salmon. Please proceed with your question.

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

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

Great. Thanks.

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

Hi, guys. Thanks for taking the questions. Just on the Alzheimer's disease agitation 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 AXS05 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 One went through some protocol amendments and was obviously concluded early? I think the messaging was that that may have been pivotal when it first started and it turns out it wasn't. I guess what has changed there to say that Accord Two would be pivotal and Accord One wasn't? Thanks.

Thanks for the questions. With regards to the open-label extension study, so we continue to enroll the open-label safety extension trial as a reminder that requires or what we're trying to do is to meet ICS guidelines, which are 300 patients treated for six months and 100 patients treated for one year and well on track to accomplish those goals. So, Accord2 does not affect that. And then also the patients who are completing Accord2 are also able to then go on and continue to be dosed. So, we're very comfortable with regards to needs and the necessary number of patients. As it relates to Accord 2 being a pivotal study, and also as comparing that to Accord 1, so what's nice about Accord 2 is we've completed Accord 1, and so all of the learnings in terms of In terms of our confidence around the endpoint, which would be necessary in a study like this, we have. We're able to design the core two very prospectively. We have also received feedback from the FDA that this could be a registration trial based on the design. I think that is the fact that Accord 2, we are designing it and we have designed it with the benefit of the knowledge from Accord 1, which is a benefit in this case. Thanks for the question.

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

Hi. Congrats on all the progress this quarter, and thanks for taking our question. On AXS14, how confident do you feel that the FDA has all it would need from a clinical efficacy perspective to approve the application? And then on CINOSI, can you just provide any additional color on the power and assumptions for the phase three trial in MDD?

Sure. Hey, I'll take 14. This is Mark. So, you know, we're targeting this quarter here, and the In terms of content, that's substantially complete. Those things are being finalized, and really it's just building out the submissions. We're going through 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 solar amphitol in MED, We powered that study similarly to the way that we powered our other studies in major progressive disorder. As you know, we do have quite a bit of experience there with the ability program. So think about the powering as being similar. And I think in general, for these studies, the effect sizes, which one would expect with these drugs, is very well laid out, and there's a lot of precedent. So that's how we power the study. So to summarize, it's 90% power to detect an effect size, which is similar to the effect size which we detected in program.

Thanks for the call.

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

Well, thank you for taking the time to join us for today's quarterly update. The first quarter of 2024 marks strong progress for Axon. 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 your day.

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