Axsome Therapeutics, Inc. ($AXSM)

So thank you for joining us again this afternoon at the Life Sciences -- Citizens Life Sciences Conference. Excited to be joined next by Axsome. I'm going to turn it over to Mark Jacobson, the Chief Operating Officer, and we're also joined by CFO, Nick Pizzie. Thank you.

Yes. Thanks very much, Jason, and thanks to the Citizens team for having us. And we'll do this in 2 parts. So Nick and I will run through a brief overview of the company, and then we'll open it up for Q&A. So thanks again for having us. And very quickly, of course, we've got obligatory forward-looking statements, and we may be making forward-looking statements today. So please review our filings with the Securities and Exchange Commission for a complete summary and overview of the risks and uncertainties associated with our business. Axsome is a commercial and clinical stage biopharmaceutical company. We are focused on central nervous system disorders, in particular, frontiers in central nervous system disorders, and our mission is to develop and deliver transformative medicines for the hundreds of millions of people impacted by CNS conditions. 2025 highlights, Nick, you want to cover those questions?

Sure. Yes. 2025 was a successful year for Axsome. We -- a couple of milestones that we hit for the year from a sales perspective was Auvelity surpassed over $0.5 billion in revenue. That was only the third year since launch. And total sales for the company were close to $640 million. So super excited. It's a nice setup for 2026 and how we're approaching on -- and the success that we've had in 2025. The biggest thing that we are looking forward to in 2026 is our PDUFA date for Auvelity in Alzheimer's disease Agitation. That PDUFA date is on April 30, 2026, so just a couple of months away. And currently, we are in the process of expanding the team from 300 to 600, which we'll get into in a bit.

Yes. And so fundamentals, just coming out of 2025, fundamentals for the business across all aspects, commercial, R&D and just the infrastructure supporting those categories of the business, it's never been better. So we're very well positioned going into, as Nick mentioned, key catalysts for the organization that are potentially transformative and just continued commercial execution. Real quick on the current state of affairs for Axsome, and we think the business is -- we're in a very unique position here. We have 3 on-market products, which are innovative and highly differentiated, two of which we fully developed internally, Auvelity and SYMBRAVO. We have 5 differentiated and novel product candidates. And of those, we are conducting 7 late-stage clinical trials, so Phase III clinical trials that are either already underway or will be initiating shortly. That's 9 of the programs that are in the portfolio, in our pipeline have blockbuster potential, and we're focusing on 11 different conditions. And those results -- and Nick, do you want to cover the potential opportunities?

Total peak sales for the conditions that Mark spoke about is north of $16 billion. And as you can see, greater than 150 million patients that these indications affect. And importantly, though, is that we have patent protection into the 2040s.

Yes. All the programs. Of those 11 programs, here's the pipeline, and we think about them as the overall umbrella is CNS, but we're very interested in unmet needs and in psychiatry and neurology. And here's how we break out the product candidate pipelines, and we'll review these in the coming...

Yes. So 3 commercial stage products in Auvelity, Sunosi and SYMBRAVO. We'll talk about peak sales shortly as it relates to them and then multiple Phase III assets that are -- that we're assuming positive clinical readouts, which we'll get into that as well shortly. We would expect a launch sometime in the late 20s and then most recently, AXS-17 to the pipeline as it relates to epilepsy indication. So here is just kind of a nice little solar system of how we think about peak sales. And as I shared earlier, about the $16 billion. So if you think about what we have already commercialized and continue to grow, it's in the neighborhood of $2 billion to $5 billion. That's that lower semi circle there. And then really what has gotten the most focus over the last, call it, several months is the AD Agitation indication with the PDUFA date of April 30, that we've shared peak sales of $1.5 billion to $3 billion for that indication alone. So if you think about Auvelity and AXS-05 is Auvelity, it'd be somewhere in the neighborhood of $2.5 billion to $6 billion. These are peak sales that we've put out prior to launch, and we'll look to assess peak sales if and when we do receive approval.

So recent -- just -- we touched on 2025 as a year of execution and transformation for the business, just reviewing some of those accomplishments and recent accomplishments so far to start this year. Obviously, the launch and -- the approval and launch of SYMBRAVO, sNDA submission of AXS-05 for Alzheimer's Disease Agitation that was accepted and filed and granted prior to review. And 2 other items to focus on with trials. So we had a number of positive trials over the past year. And then we've recently initiated the FORWARD Phase III trial of AXS-14 and fibromyalgia and then the CLARITY trial, Phase III trial of solriamfetol in major depressive disorder with individuals who have symptoms of excessive daytime sleepiness. And then looking ahead, we touched on, obviously, the sNDA PDUFA date of AXS-05 in Alzheimer's Disease Agitation over April 30. And then we have an imminent NDA submission of AXS-12 for cataplexy in narcolepsy. We're about to push the button there. We have top line trial readouts anticipated in the second half of this year for solriamfetol in binge eating disorder. That's the ENGAGE Phase III trial and then the SUSTAIN Phase III trial of solriamfetol in shift work disorder. We anticipate those top line results next year. And we'll be initiating a number of trials across the product candidate pipeline in the coming months, and we'll touch on those in the coming slides. So 2026, the 4 pillars of focus, commercial performance, number one, continue to drive growth, and we'll cover that, but we will be investing further in all elements of the business to not only continue current trajectories, but drive them further. Auvelity prepare for a launch for a potential approval. If the product is approved and advance all of the R&D programs, all 11 of them, and we'll continue to do that, and we'll look towards growth there. And supporting all of that will be continued growth in the team and infrastructure that supports the business.

So again, our 3 main products, Auvelity, Sunosi and SYMBRAVO, I'll dig deeper. We have slides for each one of these. But again, combined total peak sales of $5 billion across these 3 brands in these specific indications. Auvelity, probably the key point again is going -- is doubling the field force. We're going from 300 reps to 600 reps, and we're in the process of that recruiting. Currently, we anticipate that we'll have that completed by Q2 and ideally before the PDUFA date of April 30. Sunosi continuing to grow. We acquired that asset back in 2022, and it's been a really nice performing product for Axsome, grew 40% year-over-year in a -- with a very mild, moderate level of investment into that program. And then SYMBRAVO, we just launched that in June of 2025. So we're just getting off the launch pad there, and we're seeing some nice growth in scripts. And really, the next key driver of growth would be to improve the payer coverage.

Auvelity, very quickly, oral NMDA receptor antagonist, sigma-1 agonist. It's approved for major depressive disorder in adults; works quickly, works rapidly, sustained and a distinct tolerability profile. Very quickly, Nick touched on some elements of sales to date, but making a very quick impact as a treatment option for patients in terms of -- in the early days, later-line patients and now about 50% of utilization, just over 50% is in first or second line or so first line or first switch. More than 50% of the scripts are coming from -- as monotherapy, and we're seeing important growth in primary care. So now primary care, that makes up about 1/3 -- about 1/3 of prescribers are primary care.

And that's really a key initiative for Axsome and for Auvelity for 2026. Part of this expansion is to drive further in the primary care market. We're currently only 0.2% of the market share in total antidepressant market. So we feel that, that number can grow significantly as we get into primary care. We've been able to perform and annualize already at north of $600 million with a relatively small field force compared to some of our peers. On average, we've had somewhere in the neighborhood of 200 to 250 reps. During the course of this, we ended the year around 300 reps, just under 300 reps. But being able to annualize where we are with market access that has improved, we're currently now at 86%, which we're pleased with. We're looking to further improve and evolve that, meaning to have improved formulary access. But 86% total covered lives, of which 78% is in the commercial channel, 100% in the government channel, which is important as we'll talk about for ADA, Alzheimer's Disease Agitation, where most of the scripts will be coming in that channel. So that will be one hurdle that potentially can be avoided upon the launch of ADA, where access will be available. So the focus with going from 300 to 600 reps is we expect to be able to get that return on investment because we'll be able to -- we have the covered lives. We'll get in the primary care market. And also, we did a direct-to-consumer TV campaign in Q4, which we will look to continue on during 2026, but maybe at a different level than what we did in Q4.

Quick snapshot of sales. Do you want to touch on?

Yes, just great growth, 68% in total sales quarter-over-quarter growth Q4 to Q4 and 74% so surpassing $0.5 million in total annual sales and multiplying the $155 million by 4, north of $600 million annualized already 13 quarters in. So pleased with that growth, again with a relatively smaller field force team. But looking at comps 13 quarters in versus 13 quarters for other comps, we're outpacing them as well. So really pleased with the performance of Auvelity.

Yes. And that corresponds to the clinical profile. That's what we're seeing in the real world and the feedback we're getting from clinicians of how the treatment option for patients and prescribers is doing well. Turning to Sunosi. Nick touched on, this is a product that we acquired, and we're very pleased with how it's growing for the currently approved indications that's excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea.

Again, just continued growth. We saw 40% growth in revenue year-over-year. So demand growth has continued to grow. Thank you. And the price impact actually has been positive. So being -- seeing that 40% growth and then 33% year-over-year, while we've had this asset since second quarter of 2022, I think it was launched sometime in the late around 2018, 2019 by the predecessor. So overall, again, super healthy and basically continue to grow while we are developing it for additional indications that are much more meaningful even from a peak sales perspective compared to the current indications in $300 million to $500 million right now.

We'll obviously get into those momentarily. Then just looking at SYMBRAVO. So this is our third product candidate and the second that we developed fully. This was approved about a year ago, and we launched it, as Nick mentioned, in June of last year. So it's a multi-mechanistic, is rapidly absorbed, and it's a distinct treatment approach for the acute treatment of migraine. And this utilizes Axsome's MoSEIC technology, which drives absorption. So you get in terms of how you reach Tmax and PK dynamics underneath, which lead to rapid pain relief, which is sustained and durable with a very nice tolerability profile.

We're pleased with where we're at. SYMBRAVO is flying a little bit under the radar on a lot of investors' minds right now, which is fine. It's doing its thing. We've seen pockets in the country where it's really outperformed expectations and even peers at the same time at launch. And we are doing it with a discrete field team. We have roughly 100 reps. Some of our peers launched with 800 reps or north of that. So it's a similar playbook that we did with Auvelity out of the gate with 160 reps in a mass market. This is obviously a similar large market. And as payer access comes online and as trial and adoption increases, we're super excited about this asset. I know it doesn't get a lot of play right now with Auvelity, specifically around the ADA indication coming about, too, but looking forward to the future for SYMBRAVO.

And we like the feedback we're hearing from clinicians about the product profile and that it's aligning with the data we've demonstrated for the clinical program. And real quick, we'll touch on the pipeline, and we'll just from time constraints, we'll skip through this. We touched on AXS-05 for Alzheimer's Disease Agitation. Reminder, it's an oral NMDA receptor antagonist, and it targets a number of pathways that are relevant in agitation. This is Alzheimer's Disease Agitation, which is one of the key symptoms and concerning symptoms of individuals with Alzheimer's disease. So about 7 million people in the U.S. with Alzheimer's Disease and north of 70% of those have symptoms of agitation. And this is a critical symptom. It often is the symptom that leads to placement in long-term care facilities. And right now, a high area of unmet need. The -- there's only one approved product and the majority of treatments and interventions that are used are off-label atypical antipsychotics and antidepressants. We have an sNDA, as mentioned, that's under review by the FDA right now. This is a division of psychiatry. The application has priority review, PDUFA date, April 30. And it's got a robust clinical program supporting that. We had -- here, we highlight results from the ADVANCE-1 and ACCORD-2 trials. We have 3 positive trials that are part of the package, a stand-alone ICH safety database. And we're within -- PDUFA is less than 2 months out. So Nick touched on some of the prelaunch activities we are doing for a potential approval to be ready for that. And we're obviously very excited about this program, both from an efficacy perspective as well as the tolerability profile that we saw in the clinical program. AXS-05 is also being developed for smoking cessation. We're about to launch a Phase III trial here in the indication. We'll have more to say soon. But obviously, this is a very impactful therapeutic area and 34 million adults in the U.S. smoke. And as a result, half of them have a disease that is related to their smoking. And just the health care impact and costs are substantial. So stay tuned for updates here, and we'll be launching a study soon. Solriamfetol, as Nick touched on for Sunosi, we have 4 indications that are of interest, and these all tie to clinician feedback about the product profile and underlying mechanistic rationale for these areas of development and in particular, it is dopamine and norepinephrine reuptake inhibitor. So it's wake promoting, but we also see other changes that may be relevant to impulse control or inhibition and other sleep-related indications. Four Phase III programs, ADHD, MDD with excessive daytime sleepiness symptoms, binge eating disorder and shift work disorder. Quick status of these studies, but we'll touch on these here individually. So Attention Deficit Disorder impacts a substantial number of people in the U.S., 22 million and about 7 million are children. And for our program, we have so far completed a positive Phase III trial in adults. That's the FOCUS trial. And we will be launching 2 trials in pediatrics, so one in children, one in adolescents, and that's coming up soon. And those are the next components of the clinical program that we plan to conduct for potential label expansion efforts. MDD with excessive daytime sleepiness symptoms, we've recently -- this is a precision approach to Major Depressive Disorder -- pardon me, precision approach to Major Depressive Disorder. So approximately 50% of individuals with Major Depressive Disorder have symptoms of excessive daytime sleepiness. And we are very interested in this for Sunosi or solriamfetol in particular, given its wake-promoting effect. So this is not depression in individuals with excessive daytime sleepiness. It's the other way around. This would be for the treatment of Major Depressive Disorder with -- through a lens or component of sleep. And we do anticipate this could be a distinct indication for solriamfetol. So we completed a proof-of-concept trial. We completed that last year and have recently launched a trial -- Phase III trial here. And so we haven't guided to top line results yet, but you can expect that from us soon. Binge eating disorder, this is in a Phase III trial right now -- in the ENGAGE Phase III trial. This is solriamfetol. And again, this is -- there's a mechanistic rationale here that we are exploring, and we're excited about this study. We expect top line results in the second half of this year. And then the final clinical program that we're running is in shift work disorder. It is obviously adjacent to the current indications, which are excessive daytime sleepiness. Here, this is another element of sleep dysregulation, and we're conducting the SUSTAIN Phase III trial. We anticipate top line results next year. And we have aligned with FDA that because this is a related condition to the currently approved programs, our expectation is if the SUSTAIN trial is positive, that's the only study we need to support potential label expansion. AXS-12, and we'll be very snappy here given we're low on time. This is our product candidate reboxetine. We have completed the clinical program. We are submitting an NDA for cataplexy in narcolepsy imminently, and we're excited about this program. It fits very nicely with the Sunosi sleep field force that we have in place now. And just very quickly on the -- some of the clinical data and the clinical trials that support the package, the CONCERT and SYMPHONY trials where we saw a robust impact on cataplexy. AXS-14, this is the SS-enantiomer of reboxetine. So Esreboxetine, we have 2 completed trials, a Phase II and a Phase III trial where we saw important and robust statistically significant -- highly statistically significant results in reductions in pain and an impact on fatigue. So we've launched a Phase III trial. This is based on feedback from the FDA that they wanted to see another fixed-dose 12-week study with reboxetine. So we launched the FORWARD trial to generate the additional data that FDA has requested of this and of us, and we'll provide guidance here for when we anticipate top line after we've conducted the study for some time and we have a sense of enrollment trends. We're very excited about this program. And here's a quick snapshot of the trial design. So this is a randomized withdrawal design trial where there's a portion of open-label treatment with AXS-14 and then there's a randomized discontinuation phase. Finally, we have AXS-17, which is a new program. We recently in-licensed this. So this is a subtype selective alpha 2, 3 GABAA PAM, and we plan to develop this for epilepsy. We -- 2026 is all about Phase II enabling work, tech transfer and indication selection. So we'll have more to say on this program, in particular, the specific indication that we plan to launch, but we're pretty excited about this, and this rounds out the product candidate pipeline, which is very heavy in late-stage programs. So this starts to build out our earlier-stage pipeline. So all of the programs are protected by robust patent portfolios. And I'll just point out that AXS-12 has orphan drug designation.

Yes. So -- and everything that Mark just talked about is fully funded. That's a great thing. We're in a fantastic financial position, $323 million on the balance sheet, takes us to cash flow positivity. We've already seen quarters where we actually had cash flow positivity, specifically Q3 of 2025. So looking to further have sustained cash flow positivity and profitability shortly thereafter. Small amount of debt, around $190 million. We refinanced our loan with Hercules to Blackstone last year. Pleased with that from a cost of capital. And one of the things that we've shared is that operating leverage continues in the company. So we grew revenues 3x faster than OpEx in 2025, and we expect to have continued operating leverage in 2026 even with doing all these things, including the expansion that we're planning to do in the first half of this year. I think with that, that concludes our presentation.

Great. Thanks, guys. Really appreciate it. Let me throw a couple of questions here. The field force expansion, can you just talk to what proportion or a piece of that is focused on AD Agitation launch specifically versus, for example, you said growing the primary care exposure.

Sure. So we're going from 300 to 600. Those 600 reps will be doing ADA and MDD. So it's going to be depending on their call points and the way that we've recalibrated the geographies throughout the United States. They will have -- the reps will have MDD call points as well as ADA call points. So there's no specific reps that we focus on that. Aside from, we will have a discrete team on top of that 600 that will be calling on long-term care facilities. We currently haven't called on long-term care, significant comorbidity between -- with MDD, Depression and ADA in that space. So that team will be focused on long-term care, but likely more in the ADA market.

And there's high overlap with -- especially in primary care for those who are potential prescribers for Depression as well as AD Agitation. So each team member within the geographies will have a mix of targets for Depression, Alzheimer's Disease Agitation and both.

Obviously, just a few weeks away now from the PDUFA date for AD Agitation. I know you're not going to say a lot here, but just FDA interactions, how does feel towards the PDUFA date?

Look, it -- for where we are today, you're correct. We just, as a matter of process, don't comment on real-time day-to-day updates. But what we can share is breakthrough therapy designated, priority review granted. And a reminder, April 30 is the PDUFA date. So we're getting very close. And things are where you would expect them to be at this point in the review. And that comment is informed by our interactions with team, our field division vision into the division of psychiatry. We're not aware of material changes to the team or any changes along those lines. So it's -- again, things are where we'd expect them to be, and we're preparing for potential launch if the product is approved.

Yes. All -- everything is churning internally. We have actually a non-branded campaign website, alzgoals.com, alzgoals.com. Medical affairs team is doing its thing in preparation for the launch and marketing same thing, doing all that prep work prior to a launch.

Great. Well, Mark, I really appreciate you guys coming.

Thank you.

Thanks a lot, Jason. Thank you.