Axsome Therapeutics, Inc.

Hello, and welcome to the Axiom Therapeutics fourth quarter and full year 2023 conference call and webcast. If anyone should require operator assistance, please press star zero on your telephone keypad. A question and answer session will follow the formal presentation. You may be placed into question queue at any time by pressing star one on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Chief Operating Officer Mark Jacobson. Please go ahead, sir.

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 fourth quarter and full year of 2023. The release crossed the wire a short time ago and is available on our website at axon.com. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of our investigational agents, our clinical and non-clinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development plans, our commercial plans regarding synoviality and our 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 Tabuto, Chief Executive Officer, Nick Pizzi, Chief Financial Officer, and Ari Maizel, Executive Vice President and Head of Commercial. Ariel will provide an overview of the company and progress made in the fourth quarter of 2023, as well as key upcoming milestones. Following Aereo, Nick will review our financial results, then Ari will provide a commercial update. We will then open the line for questions, and questions will be taken in the order they are received. And with that, I will turn the call over to Aereo.

Thank you, Mark. Good morning, everyone, and thank you for joining Axon Therapeutics' fourth quarter and year-end 2023 financial results and business update conference call. 2023 was another strong year for Axone, built on focused commercial execution for our first-in-class marketing products and continued advancement and expansion of our industry-leading neuroscience pipeline. During our first full year as a commercial company, Obelody, our first-in-class oral NMDA receptor antagonist and signal-1 receptor agonist for depression, and Synose, our DNRI and colon agonist for excessive daytime sleepiness, generated combined net product revenue of approximately $205 million. We expect continued revenue growth in 2024, aided by our completed Salesforce expansion, or Velody, and increasing awareness of our differentiated products. Later in the call, Nick will provide details on our quarterly financials, and Ari will provide additional information on our commercial performance. During 2023, our innovative development pipeline also progressed and expanded. We made solid progress in the preparation of our NDAs for AXS07 in migraine and AXS14 in fibromyalgia. We advanced our Phase III trials of AXS12 in narcolepsy and AXS05 in Alzheimer's disease agitation. We initiated a Phase III trial program for sorianfetol in ADHD and announced three additional new indications for sorianfetol. This progress positions us to deliver on multiple potentially value-driving milestones throughout 2024. I will 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 in the first half of 2024. The NDE submission for AXS14 for the management of fibromyalgia is also tracking for submission in the second quarter of 2024. Now moving on to our late-stage clinical programs. We have completed enrollment in the Phase III symphony trial of AXS12 for the treatment of narcolepsy, and we are on track to report top-line results for symphony during the first quarter. For AXS05, The Phase III Advanced II Trial in the Treatment of Alzheimer's Disease Agitation is tracking for completion in the second half of 2024 based on anticipated enrollment trends and recent treatment market dynamics. Referring to solvory amphetol, the active molecule in Synose. In December, we held an Investor Day event where physician experts provided the scientific and clinical rationale underlying the exploration of solar amphetol in new target indications, including major depressive disorder, binge eating disorder, and shift work disorder. We expect to initiate phase three trials in each of these indications in the first quarter. These new trials complement the ongoing phase three focused trial of solar amphetol in adults with ADHD. FOCUS is tracking for top line results in the second half of 2024. Overall, our development portfolio encompasses five innovative, late-stage, patent-protected product candidates for 10 serious psychiatric and neurologic conditions. If successfully developed, these investigational medicines have 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. alone. I will now turn the call to Nick, who will provide details of our financial performance.

Thank you, Ariel, and good morning. Today, we'll discuss our fourth quarter and full year results and provide some financial guidance. Total product revenues were $71.5 million and $204.9 million for the fourth quarter and full year of 2023, representing year-over-year growth of 193% and 309%, respectively. This consisted of net product sales of $70.7 million and $202.5 million for the fourth quarter and full year of 2023, and royalty revenue of $800,000 and $2.4 million, respectively. Total product revenues for the comparable periods in 2022 were $24.4 million and $50 million. Total revenue for the full year of 2023 was $270.6 million, which includes license revenue of $65.7 million from out-licensing Synosi in certain ex-U.S. territories. Avelity net product sales were $49 million and $130.1 million for the fourth quarter and full year of 2023, respectively, representing the first full year of commercialization for Avelity. Ovelity was launched on October 19, 2022, and had U.S. net sales of $5.2 million for the fourth quarter of 2022. The NOSI net product revenues were $22.5 million and $74.8 million for the fourth quarter and full year of 2023, representing 17% and 67% year-over-year growth, respectively, and consisting of $21.7 million and $72.4 million in net product sales, and $800,000 and $2.4 million in royalty revenue associated with Cenosi sales in outlicensed territories, respectively. Cenosi net sales for the comparable periods in 2022 were $19.2 million and $44.9 million. Total Cenosi revenue for the full year of 2023 was $140.5 million, which includes a license revenue of $65.7 million from outlicensing Cenosi in certain XUS territories. Total cost of revenues were $7.4 million and $26.1 million for the fourth quarter and full year of 2023. Total cost of revenue for the comparable periods in 2022 were $2.3 million and $5.2 million. Total cost of revenue for the full year of 2023 included a one-time cost of $5 million associated with the revenue received on outlicensing CINOSI in certain ex-U.S. territories. Research and development expenses were $30.8 million and $97.9 million for the fourth quarter and full year of 2023, respectively, compared to $14.7 million and $57.9 million for the comparable periods in 2022. The increase was primarily related to the focused trial of Solvri Ampetol and ADHD, the advancement of ongoing trials of AXS05 and AXS12, manufacturing costs associated with the anticipated NDAs for AXS07 and AXS14, Post-marketing commitments for both Avelity and Synosy, and higher personnel costs, including non-cash stock-based compensation. Selling, general, and administrative expenses were $86.8 million and $323.1 million for the fourth quarter and full year of 2023, respectively, compared to $61.5 million and $159.3 million for the comparable periods in 2022. The increase was primarily related to commercialization activities for Avelity and Synosi, including Salesforce and marketing expenses, and higher personnel costs related to organizational growth, including non-cash stock-based compensation. Net loss for the fourth quarter of 2023 was $98.7 million, or $2.08 per share, compared to a net loss of $61.2 million, or $1.41 per share, for the comparable period in 2022. The net loss in the fourth quarter of 2023 includes $63.7 million in non-cash charges, comprised of $43.2 million in acquisition-related contingent consideration expense, reflecting our updated sales predictions or recently announced new indications for salary impotence, $18.9 million for non-cash stock-based compensation expense, and $1.6 million of non-cash intangible asset amortizations. net loss was $239.2 million, or $5.27 per share for the full year of 2023, compared to a net loss of $187.1 million, or $4.60 per share for the full year of 2022. The net loss for the full year includes total non-cash charges of $117.9 million, which includes $62.6 million of stock compensation expense, $48.9 million in fair value of contingent consideration expense, and $6.4 million in intangible amortization compared to $37.7 million, $3.3 million, and $4.1 million, respectively, for the full year of 2022. Avelity and Senosi GTN discount in Q4 of 2023 were both approximately 50%. Q1 typically has a negative seasonality effect on GTN. As a reminder, the GTN discount for availability in Q1 of 2023 was in the high to upper 50s and in the mid 50s for Synose due to the seasonal Q1 GTN dynamics. We would therefore expect a similar GTN in Q1 of 2024 for both products. We ended 2023 with $386.2 million in cash and cash equivalents compared to $200.8 million at December 31st of 2022. 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.

Thank you, Nick. Axiom completed our first full year as a commercial company by delivering strong performance for both of our on-market products, starting with Ovelity. In the fourth quarter, approximately 84,000 prescriptions were written for Ovality, representing 23% quarter-over-quarter growth. This performance contrasts with a decline of 1% for the overall antidepressant market during the same period. Additionally, nearly 17,000 new patients started Ovality in the quarter, bringing the total number of unique patients treated with Ovality since launch to approximately 71,000. In the fourth quarter, more than 3,500 first-time Ovelity prescribers were activated by our sales team, increasing the cumulative total number of prescribers since launch to nearly 17,000. Payer coverage was stable in Q4, as Ovelity remains accessible to patients representing approximately 70% of covered lives. We continue to progress in conversations with major plans and PBMs across all channels, as we pursue access improvements for patients. Availability performance in the quarter was primarily driven by specialists in psychiatry practices, with both psychiatry MDs and nurse practitioners and physicians assistants, or NPPAs, contributing to robust growth in the quarter and over the course of 2023. In addition, we observed meaningful traction within the primary care segment among both MDs and NPPAs. as the early impact from our recent Salesforce expansion began to take hold with increased call activity in primary care offices. In a recent survey of providers in psychiatry and primary care who treat a significant proportion of depression patients, key drivers of ability prescribing cited by respondents include rapid onset of action and low impact on weight gain and sexual dysfunction. In addition, Adopters note the positive impact ability has demonstrated on day-to-day patient functioning and its improvements in patient perceptions of quality of life. Axone has established a strong commercial foundation to support continued ability growth in 2024. With approximately 260 sales representatives calling on 44,000 healthcare providers, and continued investment in our industry-leading digital-centric commercialization platform, we are well-positioned to accelerate our education and awareness objectives across the predominant depression treaters in the U.S. An enhanced brand story for 2024 has been created to augment provider perceptions of ability and is anchored on ability's key attributes. Ability is a rapid-acting antidepressant that works fast and lasts. with rapid symptom improvement observed at week one, substantial symptom improvement observed at week two, and both sustained and substantial symptom improvement observed at week six. Availability has a well-established safety and tolerability profile that includes low impact on weight and sexual dysfunction and no risk of movement disorders or extrapyramidal symptoms. Further, Alveolity is the only oral antidepressant that modulates both glutamatergic and monoaminergic pathways, a key point of consideration as the role of glutamate in depression is increasingly understood and accepted across the clinician landscape. We are very optimistic about Alveolity's growth prospects in 2024 and its long-term blockbuster potential. Transitioning now to Synosy. Total prescriptions were just over 42,000, representing 2% sequential quarterly growth and 18% growth versus Q4 2022. Approximately 3,600 new patients started Synozid treatment during the quarter, bringing the total number of unique patients treated with Synozid to 65,000 since launch. Although excessive daytime sleepiness is a smaller market with a more limited prescriber base, we continue to activate new prescribers. including more than 400 during the fourth quarter alone, for a total cumulative prescriber base of more than 12,000 since launch. The field team is focused on communicating the needed urgency to treat excessive daytime sleepiness symptoms in obstructive sleep apnea and narcolepsy, with disproportionate focus on the nearly 2,000 active weekly prescribers in the space. Payer coverage for Synozy was consistent in Q4, with a total of 83% of lives covered across all channels. In a recent survey of Synozy adopters, key attributes driving demand for the product cited by respondents include significant and sustained impact on the F-word sleepiness scale, a market-leading 9-plus hours of wakefulness observed in Phase III clinical trials, and significant improvement in patient-reported outcomes at Week 12. We are very proud of our commercial effort for Synozy and expect continued growth in 2024. In closing, Axome delivered compelling commercial performance in Q4 2023 as the optimization of our commercial infrastructure took shape and we completed our first full year as a commercial company. Anecdotal feedback from providers and patients continues to reinforce our belief that Ovelity and Synozy our unique and differentiated treatment options and their respective indications, and supports our growing confidence that Axome is reshaping the treatment landscape for CNS conditions. I will now turn the call back to Mark for Q&A.

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

Thank you. We'll now be conducting a question and answer session. If you'd like to be placed in the question queue, please press star 1 on your telephone keypad. you may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing star one. Our first question today is coming from Leonid Timishev from RBC Capital Markets. Your line is now live.

Thanks for taking my question. Maybe I'll start off with a question on the advanced two readout. I guess, can you maybe provide a little bit more color on What drove the slip in timelines? I guess what's driving the slower recruitment? Is there any reflection on the potential market opportunity from that? And any risks to trial integrity, especially as standard of care evolves? Thanks.

Well, thank you for that question. I think the second part of your question, which is the evolving nature of the standard of care, that's really what is driving this. This is an indication that we're really excited about. And we did want to take into account the recent launch of brexpiprozole and any potential impact that could have on enrollment. As a reminder, brexpiprozole is the first drug that is approved in this indication. So our internal analytics team has been monitoring very closely the prescription trends. And what we've seen is a clear inflection in prescribing, which we attribute to that new indication. So our revised guidance incorporates this new information. Having said that, we're confident that we should be able to deliver data this year. Are any further comments about the evolving treatment landscape in BREX?

Yeah, I would just say, you know, related to the BREX triptozol increase, we're seeing a substantial increase across the Medicare channel, which we tie directly to the ADA indication. But I think this is also really positive news for AHS-05. Clearly, there's significant unmet treatment needs, and that gives us great confidence for the future with AHS-05.

Got it.

Thank you. Thank you. Next question today is coming from Charles Duncan from Cantor Fitzgerald. Your line is now live. Hey.

Yeah, morning, Ariel and team. Congrats on a great year of commercialization. I did want to follow up on a question on AXS05. But first, with regard to commercial performance for Ability, I'm wondering if you can provide any sense of persistence. I know it may be a little bit too long, but you mentioned for the branding, you know, fast and last in terms of activity. I'm wondering what you can see in terms of performance refills in patients staying on drugs.

Thanks for the question, Charles. It's still a little too early to share any information on persistency and adherence. What I will say is the feedback we're receiving from patients and clinicians suggests that the clinical profile from Phase 3 is holding up in the real world. So, we expect to generate additional data in the future. But for now, I'd like to say that what we're seeing in the real world is reflective of the Phase III clinical trial results.

Okay, that's helpful. And if I could follow on to the last question regarding AXS05 and ADVANCE2. I'm wondering if you have any changed, you know, perspective on the probability of success given Otsuka's 786 data recently? And then also, in terms of the open label extension, are patients enrolling into that? And how does that appear to be going? Maybe, yeah, just kind of broadly.

Yeah, thanks for the questions, Charles. With regards to the Otsuka readout, we don't think that that has any meaningful read-through to our product. Now, we watch any data readout or any developments in the space for any potential learnings to our clinical development. However, we think that the best data to look at when you're thinking about the potential of XSO5 and Alzheimer's disease agitation is the data that we've generated with our own product. And as a reminder, We have now completed two phase three trials which were placebo controlled, both of which had positive results. So we think that that is information which is more relevant than information with other molecules. And if you then take it one step down and actually look at the products themselves, they are different molecules entirely. ABP-786, as a reminder, is a deuterium-modified dextromethorphan, whereas the XSO5 incorporates a non-deuterium-modified dextromethorphan. And the inhibitors also are different. So we use an aminoketone, and then they use quinidine. So very different. And as it relates to the open-label safety extension trial, that is going well. And The vast majority of patients who are rolling out of our Advanced True Trial are opting to go into the Open Label Safety Extension. We think that that is a good indicator of how the caregivers are thinking about the product.

Okay, very good. Thanks for the added color, Ariel. I'll hop back in the queue.

Thank you. Next question is coming from Ash Verma from UBS. Your line is now live.

Thanks for taking our questions. I have two, both on AD agitation. So maybe just on the advanced two study, are you trying to recruit naive patient to treatment, and that's why you want to kind of exclude anyone who has started therapy on Rixaldi? That's the first one. And then second, like actually, Just fast-forwarding to when you assumed that this would come to the market, would you need to primarily focus on the long-term care facilities where a lot of these patients broadly reside? And just curious what type of sales footprint that might require versus I think your DCC platform is kind of more like footprint. Thanks.

So thank you for the question. The answer is yes, we are recruiting primarily naive patients, and we would want to exclude folks who are on Rexalty for obvious reasons. And then our revised guidance does take into account any potential impact on losing patients because now patients do have a treatment option which is approved. And in terms of long-term care facilities, our studies thus far have been conducted in the community setting. We think that that's where the majority of patients reside who have this indication. And one of the things that we're excited about as it relates to the profile of SSO5 in Alzheimer's disease agitation is that it could potentially keep patients out of long-term care facilities. In other words, keep them at home with their loved ones.

Thank you. Next question is coming from June Lee from Truist Securities. Your line is now live.

Good morning. This is an awesome one for June. Thanks for taking the questions. I was wondering if you could comment on what the breakdown of patients on availability currently is, around what percent are first line. And then also just I want to clarify, is the expanded sales force fully online now and can you comment on if you think current PRX trends are reflective of the full 250-person sales force? Thank you.

Well, thanks. I'll turn that over to Ari.

Hi, thanks for the question. So we are seeing a meaningful improvement in terms of earlier line treatment. Over the course of 2023, we saw meaningful increases in first and second line treatment every quarter. So today, there's roughly 40 to 50% of patients receiving availability in the first or second line setting. We expect that trend to continue over time. Regarding your Salesforce expansion question, we are fully complete with the expansion. We hired the additional representatives at the end of last year, completed training in January of this year. We're starting to see meaningful impact in terms of call activity. In particular, we're seeing an increase proportionally of calls to the primary care segment. We would expect the TRX and NBRX trends to continue to increase over the course of the year, and there will be a ramp beginning in Q1. And so more details to come, but we are very pleased with the increased field force after post-expansion. Thank you.

Thank you. Next question is coming from Jason Gerberry from Bank of America. Your line is now live.

Hey, guys. Good morning. Thanks for taking my questions. I just wanted to follow up on the ADA enrollment dynamic with Rick Salty. I guess when we look at growth of this brand on a TRX basis, that inflection doesn't seem obvious. So I'm wondering if we should be looking at a different metric to gauge that inflection. I don't know if it's patient enrollment forms or claims, but given that it's a massive market, I'm a little surprised that, you know, given the TRX move that we've seen, that it's being characterized as an inflection. And then Is the expectation still that you get both long-term safety and efficacy data in second half, and then you'd be able to file in second half? Just wondering if the filing timeline is still on track. Thanks.

Thanks for the question. We have not given guidance on filing, so that's going to be determined by the completion of our long-term safety extension trial. That's the gain factor there. And with regards to what we're seeing from our internal analytics team on Rexalti, I'll turn it over to Ari.

Yeah, thanks, Jason. My suggestion and what we've been looking at is claims-based data by payer channel, and our observation is that breast care result is increasing significantly within the Medicare channel. So that is what we attribute the growth to the ADA indication to. Okay, thank you.

Thank you. Our next question is coming from David Anselm from Piper Sandler. Your line is now live.

Hey, thanks. So just a couple. First, on AD agitation, can you talk about the potential for branding it differently from Avelity and pricing it differently, just given that it's a Medicare Part D market and obviously different? from the depression landscape. So that's number one. Then number two, a couple just on riboxetine. One, can you talk about the timeline to an NDA and gating factors beyond the study to an NDA filing in narcolepsy, cataplexy? And then how are you thinking about pricing in that market? You've got on one end of the spectrum, pitolicin, yet on the other end of the spectrum, solar amphitol. in narcolepsy. So how are you thinking about that? Thank you.

Sure. So a couple of questions there around branding and pricing for both products. And, you know, all that already provides some color on how we're thinking about those two things. I will preview it by saying that, you know, obviously we're thinking about what we will do there and what our options are. And we would not be able to comment too much until we make a final determination. And as it relates to IFSS 12 in narcolepsy and the NDA timing, the gaining factor there will be our long-term safety extension trial. So we're monitoring that. That is enrolling. And so we need to complete that and have that read out in order to complete our package for the NBA?

Yeah, thanks for the question. Regarding the branding and pricing dynamics for ASSO5, we're currently performing an analysis to better understand the potential impact of having the same brand or different brands. And there are a lot of considerations that will go into it, including, you know, ensuring clarity around patient dosing administration, potential halo effect associated with multiple indications, the fact that there's comorbid depression in roughly 40% of Alzheimer's patients. So there are a lot of considerations, and we'll share more details in the future. And regarding the riboxazine pricing, that's another area of analysis that we're currently exploring, and we'll share additional details in the future.

Thank you. Thank you. Our next question today is coming from Joseph Tomey from TD Cowan. Your line is now live.

Hi there. Good morning, and thank you for taking my questions. Maybe the first one on AXS-12. I know the AXS-12 study is really only empowered for cataplexy, and it's a little unclear if we're going to actually get the sleepiness scores, but can you talk a little bit from a clinician perspective? Is it important to also see a signal on sleepiness in addition to cataplexy, or can you come in with another therapeutic like Synose to address the sleepiness component? And then second, on synosy in MDD, how should we be thinking about timelines to data on that? If I remember, Gemini took about six months from first patient dose to actually seeing data. So is it possible that we could see synosy MDD data this year, or what are kind of the main differences between Gemini and this study that would make that potentially not the case?

Thank you. Thanks for the questions. With regards to AXS-12, And we're very close to a data readout. So, you know, we'll refrain from making any comments around that. Look, you know, we're so close, and we'll know very soon what the profile is in the phase three trials. Now, we do think that the product should have a favorable placement in the treatment paradigm that complements Solvay Amphetol and other treatment options. We're looking forward to the data readout because that will provide us in the first phase three data to complement the phase two data that we've generated thus far. And in terms of Synozy with regards to MDD, we'll have more to say about that hopefully once we announce enrollment of the first patient in that study. That remains on track to start this quarter.

Great, thank you.

Thank you. As a reminder, that's star one to be placed in the question queue. Our next question is coming from Mark Goodman from Learing Partners. Your line is now live.

Yes, good morning. Nick, can you talk about how we're thinking about spending this year? And then secondly, you talk about how you have enough cash to get to cash flow positivity. Can you give us a sense of when that is? And then secondly, Ariel, are you willing to give us a sense of what percent of the AD agitation study is enrolled? Are you 50, 60, 70 percent? Maybe you can give us a sense of that. Thanks.

Sure.

Yeah, thanks, Mark. So as for R&D, our expense for the quarter was $31 million, just under $31 million for Q4. That picked up slightly from the previous quarter. We expect R&D spend to increase gradually as solar re-emptile phase three trials commence during the year. This increase will also be offset, though, by lower clinical costs as the Symphony Advance 2 and Focus trials complete in 2024. And also, once AXS-14 and AXS-07 NDAs are filed. As for the SG&A line, total expense for the quarter was just under $87 million. That was also a slight increase from the previous quarter. As you know, as we mentioned, the biggest increase in SG&A was due to the Salesforce expansion, which took place throughout Q4. As that expansion occurred throughout the quarter, roughly half of the quarter's expense for that expansion was realized in Q4, so we would expect a slight increase in Q1 as we will realize the full burden of that expansion. So, and then from a cash flow positivity or profitability, you know, we are still at the early stages of the availability launch and a bit more than a year removed from the acquisition of Senosi. You know, we've modeled various scenarios and based on Based on the success that we've had thus far, we feel very confident of our ability to be cashflow positive. As you're aware, the launches by nature are very volatile. And as such, we haven't provided any guidance on specific timeline for cashflow positivity. Ariel, do you wanna take the next question?

Yeah, no, thanks, Mark, for the other question. We haven't provided the specific percentage enrollment in our trials lately, however, weighty agitation, we're confident that we should be able to have results this year.

Thank you. Operator, next question. Yep, our next question is coming from Greg . From Missouri Homeland Security, your line is now live. Greg, your line is now live. Perhaps your phone is on mute. Go ahead, Greg. Your line is now live. Yes, please go ahead. Thank you.

Okay, great. Thanks. So sorry about that. Congrats on the quarter. Just two questions. One, can you comment on the mobility DTC efforts and any thoughts around how that effort might evolve in 2024 and your level of satisfaction with what you've done so far? and what's needed on a go-forward basis. And then secondly, just as we think about the potential of Surrey Amphitel and MDD, could you just remind us on how we should think about the differential positioning of that product with Ovelity? Thanks.

Hey, Greg. Thanks so much. This is Ari. Appreciate the question. As you know, we do have a DTC effort today largely focused on digital engagement. We've been very pleased with that investment so far. What we observe through market research is nearly 8 in 10 patients who ask for ability receive it. And so we're very optimistic about continued investment in consumer advertising. And we are assessing additional investments. at the moment, and so we would expect to share some updates later in the year based on whether we intend to increase the investment around consumer advertising. As it relates to psoriasis and MDD, as you know, MDD is a highly heterogeneous condition. Not all patients respond to the same types of treatments. And because there are overlapping symptoms with other illnesses, in particular symptoms that may be more difficult for some patients than others, there's usually room for multiple treatment options to help these patients. And so until we have more data around solar amphetol and MDD, it's a little premature to talk about co-positioning with alveolity. But based on our experience, in this space, we do believe that there will be opportunities for both products to help patients achieve meaningful symptom relief.

Thank you.

Thank you. Next question is coming from David Hong from Citigroup. Your line is now live.

Hi. Good morning, and thanks for taking the questions. Congrats on the quarter. So maybe just two for me. First on Ovelity, could you provide any color around your ongoing payer discussions in the commercial channel and expectations to improve the coverage there above the current, I think, 48% or so of covered lives? And then regarding psori-amphetol in ADHD, once the results of the FOCUS study are in hand, what else would be needed to proceed to an SNDA filing there if those results are positive? Thanks so much.

Sure. So, we'll take the questions in reverse order. For psori-amphetol, the FOCUS study is in adults, and we will be launching a phase three trial in the pediatric population. So, both of those studies, both of those patient populations are needed for an NDU filing.

Yeah, and related to the payer discussions, as you mentioned, we have roughly 48% coverage in commercial channels, 70% overall across channels. The way we think about the payer is we are taking a very disciplined approach to contracting to preserve long-term profitability for our products. However, we do anticipate expanding coverage over time and remain actively engaged with health insurers to improve access for insured patients. I will mention that our current investments in both patient savings programs as well as reimbursement services will support continued prescription growth at current levels of coverage, which, as I mentioned before, remains 70% lives for all values.

Thank you. Our next question is coming from Miles Minter from William Blair. Your line is now live.

Hey, thanks for taking the questions. Just on the Tevaranda filings that I know are active, I noticed that you've recently got some new IP listed in the FDA Orange Book where the patent expires at 2043. Have you got Chapter 4 filings against those patents that we might not be aware of? And then secondly, just back on the 48% coverage in the commercial channel, that's flat quarter over quarter, yet your conversations are progressing. What is the sticking point with some of these major payers that have yet to get online with a valet at the moment? Is it more about formulary positioning, risk benefit, or is it simply just coming down to price? Thanks. Thanks.

Yeah, thank you for the question. This is Hunter Murdock. So yeah, we do have patents going out to 2043, and we do have paragraph four filings against them, which we filed suit against. So it is public information that we do have those three paragraph four certifications relating to 2043 patents.

So that's that with the type of litigation. And this is Ari. Regarding your comment on the 48%, yes, it is stable quarter over quarter. You know, every payer discussion is different. In some cases, it's related to ultimate price. In some cases, it's related to utilization management parameters. And so we are progressing those conversations. We're having meaningful discussions, but it takes time. And there are ongoing negotiations, and hopefully we'll be able to share some updates next quarter.

Okay. Thanks for the questions. Congrats on the year.

Thank you. Our next question today is coming from Yatin Seneja from Guggenheim Security. Your line is now live.

Hey, guys. Thanks for taking my question. This is Eddie on for Yachtin this morning. Regarding that Bextip result increase in the long-term care channel since their ADA approval, is that a good comment for how the availability launch could inflect on upon approval, or does the different safety profile or black spot warnings make availability more attractive? option for this population? And then what additional commercial infrastructure would you need to see that kind of inflection like Brexiprazole saw if approved? Thanks.

Yeah, thanks for the question. Just one clarification. We don't have data to suggest increase in Brexiprazole in long-term care. It's in the Medicare channel. And so, you know, I think additional data would be needed to understand whether it's in the long-term care setting or in outpatient. And I do think it's a little premature to suggest that it's a good analog for AXS05. These products do have different clinical profiles. AXS05 is a non-atypical antipsychotic. It has a slightly different profile overall. And we expect there to be meaningful growth within that indication if approved in both the outpatient settings as well as long-term care. As Ariel suggested earlier in our trials, we are focused in outpatient settings with a hope to delay patients going to long-term care facilities. In terms of commercial infrastructure, we're obviously evaluating our sales force size and structure relative to the overall pipeline. And we do expect to have a meaningful presence in long-term care facilities. However, our existing sales force is primarily focused on outpatient care practices, which we expect will continue even for ADA. So more details to come, but we feel very confident that we'll be able to have an efficient selling effort based on the shared call points for most of the indications that exist in our pipeline as well as our on-market products. Great. Thanks, and congrats again.

Thank you. We have time for questions from two more analysts. Our next question is coming from Matt Kaplan from Lannenberg Bauman. Your line is now live.

Hi. Thanks for taking the question, and good morning, guys. Just maybe a question for Ari in terms of now that you've completed the Salesforce expansion, When should we start to see an impact of that new Salesforce? And I guess over the course of the year, is it really first half or second half when we start to see them gaining traction?

Yeah, thank you for the question. We expect to see a ramp in terms of impact over the course of the year. Obviously, you know, the majority of the expansion projects Representatives were hired late last year. We completed training in January of this year. It takes time to go through call cycles and to build confidence with the brand stories and messaging and also to expand our reach into the primary care setting. And so we expect the bill to occur over the course of the year. We're starting to see some meaningful impact in terms of call activity, and we would expect demand trends to have corresponding increases over the course of the year.

Okay, that's helpful. And then maybe a question for Ariel. You gave some added detail in terms of what is necessary for filing SNDA and ADHD. In terms of the other indications you're pursuing in phase three for salivary amputal, MDD, benjening disorder, and shift work, what would be necessary there? They all include two phase three trials, or could some be with one?

Sure. With regards to salivary amputal in MDD, so there we anticipate that we would need two phase three trials. So we're launching our first phase three trial. As you know, this quarter, binge eating disorder. Similarly, we anticipate that we need two phase three trials, and we're also on track to launch the first phase three trial this quarter. For shift work disorder, we only need one phase three trial to file an SMDA.

All right. Well, thanks for taking questions, guys.

Thank you. Our final question today is coming from Vikram Porehit from Morgan Stanley. Your line is now live. Vikram, perhaps your phone is on mute.

Hi, good morning. Can you hear me?

Please proceed. Yes.

Thank you. Good morning. Thanks for taking our questions. So we had two commercial questions, one on ADA, one on MDD. So for ADA, assuming Advance 2 is positive, and AXS05 is approved for the indication, what would you expect the annual duration of therapy to be in this setting, given the potential differences in the number and duration of agitation episodes that patients with AD can experience? And then secondly, in MDD, do you think ability sales guidance is a possibility this year? And if so, what are some of the metrics and aspects of the launch that you're monitoring to gauge whether guidance is reasonable to provide? Thanks.

Thanks for the questions. With regards to duration of treatment in Alzheimer's disease agitation, so Alzheimer's disease agitation is viewed as a chronic condition, and that's how we've been studying it, and that is also reflective of how the FDA thinks about it from feedback that we've gotten from them. We do have, as you know, a long-term open-label safety extension trial, which is ongoing. So patients have been on Grug now for a fairly long time. So the study, it's a one-year trial.

Yeah, sure. Vickram, hey, this is Nick. As it relates to the sales guidance, given the relatively short period of time since launch and evolving dynamics, including the increase in sales force effort, as well as variability with market access, we're not ready to provide forward-looking guidance on sales, which is likely the case for the entirety of 2024 at this point. Got it. Thank you.

Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to management for further or closing comments.

Well, thank you for taking the time to join us for today's quarterly update. 2023 was a strong year for Axon. We enter 2024 with a growing commercial business and a late-stage neuroscience pipeline that encompasses five innovative product candidates in development and 10 serious neuropsychiatry indications. We look forward to providing multiple updates throughout the year on our progress. Thank you, and have a great rest of your day.

Thank you. That does conclude today's teleconference webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.