The William Blair 45th Annual Growth Stock Conference. My name is Myles Minter. I'm a Senior Biotech Analyst here at the firm. I cover the neurosciences and genetic medicines, and Axsome's been a day one coverage company for me. Early 2017, before the Ascend data actually was picked up coverage there, obviously a bona fide growth story with Auvelity well underway, a launch of a novel antidepressant here, and SUNOSIi really coming into its own as well. I have with me here Mark Jacobson, the Chief Operating Officer of the company, who's just about to go into the launch of their third product, actually. He's going to give us a little bit of run-through of Axsome and where they sit today, which is a vastly different story from 2017. Thanks very much. I will say, before Mark gets started, important disclosures are available at williamblair.com.
Hand it over to you, Mark.
Thanks, Myles. Good morning, everyone.
Develop and deliver innovative, transformative medicines for the millions of people, the hundreds of millions of people in the U.S. and globally who are living or impacted, living with or impacted by CNS conditions. We think about that in a few different ways. We think about, in particular, delivering innovative treatments for areas of unmet need. When I say we think about that in different ways, that means indications like Alzheimer's disease agitation, where until recently there was nothing approved and there's only one product currently approved, to other indications where there are multiple products approved, such as migraine, however patient outcomes are lacking or not where they should be, or there's been little innovation. We think about our—we'll run through the pipeline and portfolio, but we think about CNS as two broad categories: psychiatry and neurology.
We have a deep and broad pipeline within each category. Psychiatry, depression, Alzheimer's disease agitation, ADHD, binge eating disorder, and smoking cessation. Neurology, obstructive sleep apnea, migraine, narcolepsy, fibromyalgia, and shift work disorder. We will touch on this, but there is high overlap between a number of these indications, and hence the platform that we are building on the R&D side and also the commercial side. All in all, these indications impact over 150 million lives in the U.S. The way we think about impacting these indications, there are five pillars of innovation the way we think about it. First, novel or first-in-class mechanisms of action. Different differentiated treatment options at the mechanistic level. We also think about the confluence of multiple mechanisms simultaneously for an indication. We will get into the specifics here.
One area in particular that we focus on is Metabolic Pharmacokinetic modulation. That is using the body to modulate its own metabolism of APIs, drug substances, to elicit differentiated Pharmacodynamic outcomes. Clinical trial innovation, psychiatry in particular, is very difficult to detect treatment differences, high, high rates of placebo response. We also innovate on the clinical trial design and experimentation design to allow us to detect treatment signals or to give ourselves a better shot at it. We also have molecular innovation with respect to drug delivery. Where is the company today? Myles mentioned that the company is in a dramatically different place from when he started following the coverage. The company, when he initiated it in 2017, is much, much different. We have three commercial programs now, two of which we developed from scratch in-house.
The idea was born at Axsome, took it through the clinical and regulatory stages, and one of which is launched. That's Auvelity for major depressive disorder. The other is launching this month or will become commercially available. That is SYMBRAVO for migraine. We have three NDA stage programs. We'll talk about those four programs in addition to the NDA stage programs in ongoing phase III clinical development. Taken together, that positions us to have seven potential new products or new indications to the existing products by 2027. Just a fantastic time for the company, highly diversified in all aspects of the business and currently in a phase of high growth. Here's the pipeline. Again, we break it into psychiatry and neurology. I will run through the different programs, and I'll try and touch on all those today with the time that we have.
In totality, we think this is a singular pipeline with respect to CNS in the industry. Again, I'll touch on the current state of affairs for each program. All of those programs, they position us to have a potential peak sales of $16.5 billion. If you look at just the products that are approved today, so Auvelity, SUNOSI, and SYMBRAVO, potential peak sales are $ .5 billion. Just fantastic potential for the company. Again, it's a very exciting time for us. If we deliver innovation to patients and we do that in a sound business fashion, we'll deliver high returns to shareholders. 2025, already, it feels like we've already had a full year under our belt for the company and macro as well.
Just to look at what we've done so far this year, SYMBRAVO was approved at the start of the year, the end of January. We've had a number of clinical phase III trial readouts, which were positive. We had EMERGE phase III trial of SYMBRAVO. That's in oral CGRP non-responders. That was a positive study. We had two phase III trials for Solriamfetol. One is FOCUS phase III trial in adult ADHD. That study was positive. I'll talk about next steps. We had a proof-of-concept trial we call the PARADIGM Trial of Solriamfetol in major depressive disorder. I'll talk about that as well. The results there facilitate continued development in that indication. The balance of 2025 and beyond, we have the launch of SYMBRAVO. I touched on that. We expect that to be this month.
The three NDA stage programs we expect in first half, so soon, to hear from FDA on a filing acceptance decision. That is an acceptance decision with respect to our NDA submission of AXS-14 in fibromyalgia. We are on track for the sNDA for AXS-05 in Alzheimer's disease agitation for a 3Q submission, and then an NDA submission of AXS-12 in narcolepsy. Ongoing phase III trials of Solriamfetol in binge eating disorder and excessive sleepiness associated with shift work disorder. Those are moving along, enrollment is continuing, and we expect results next year. We will be starting a number of trials this year as well, a number of phase III trials. I'll cover that. Commercial side of the business, three products. Auvelity, that's our product for major depressive disorder.
That is one of the two, as I mentioned, that we developed in-house and took through approval and launch. High growth right now. It's just over two years on the market. It's growing rapidly. I'll touch on that. We're very pleased with the progress to date. SUNOSI, that is growing steadily. I'll touch on that. That is the product approved for excessive daytime sleepiness in narcolepsy and OSA. We have SYMBRAVO , which is approved for the acute treatment of migraine in adults with or without aura. Just one more time, that'll be launching, we expect, this month. Auvelity, so it's a rapid-acting oral NMDA receptor antagonist. We have some callouts of the data that were generated and the product profile. What is it? It's fast and it lasts.
We're seeing that in terms of differentiated treatment outcomes and then the underlying demand and then the growth of scripts for the product. One thing I will just point out here is that already about 50% of the prescriptions are either first or second line. We're very pleased with how it's being used. HCPs are bringing the product up in the treatment PARADIGM or treatment algorithm, which we think is a great sign. As you can see, the total scripts, just high growth at this point in time. It's currently, as of Q1, annual current run rate annually of about $400 million. It's well on the way to our target peak sales of $1 billion-$3 billion in MDD. One thing I will touch on is just some potential drivers for continued growth.
In the first quarter, we expanded the sales team to 300 account managers. It was at about 260, so we added about 40 additional more. That allows us to go further into primary care. We'd expect, so we're starting to see impact in terms of new-to-brand scripts. We expect that to continue through the balance of the year. Other drivers are continued improvements and evolution in market access and coverage in the commercial channel. We are also preparing for a potential national DTC effort. That would be, if that's something we would do, it would be the second half of this year or thereafter. The team is monitoring the market right now, and we'll make a decision, a deployment decision, and we'll keep everyone posted on that.
SUNOSI, that is a first and only dopamine and norepinephrine reuptake inhibitor approved for excessive daytime sleepiness in narcolepsy and OSA. That product is growing steadily. We're very pleased. We're pleased with the feedback we get from HCPs for how patients do on the product. We see that here, especially with a very healthy business, the field force. I'll just comment on that because the field force here, it's a smaller field force there, and it's about 75 account managers. I'll comment on the SYMBRAVO field force as well. Current status quo is steady growth. I will talk about the efforts on the development side for potential label expansion for SUNOSI. You can see annualizing at about a $100 million run rate. We're pleased with that. SYMBRAVO, one more time for good measure. We'll be launching that, we expect, this month.
What is important here with respect to the product profile is the efficacy that was demonstrated in the clinical development program. That was across a variety of migraine severities. That is very important: mild, moderate, and severe. We saw robust responses in terms of pain freedom, sustained pain freedom, freedom from most bothersome symptom, and ability to return to normal functioning. We are excited to launch that. Launch ready. Launch prep, it is essentially T minus just a few weeks here. Stay tuned for the formal update. The migraine, there are a number of, obviously, there are a number of products approved, but overwhelmingly, 80% of patients are highly dissatisfied with treatment options now because they just do not address most bothersome symptom or durable pain freedom or enough pain freedom from the migraine, which are debilitating attacks. All right.
That's the quick summary of the commercial side of the house. If turning to the development side, first and foremost, AXS-05 for Alzheimer's disease agitation. This program is something that we've been working on for a number of years, and the clinical studies are done. I'll touch on that. Alzheimer's disease agitation is one of the critical symptoms of Alzheimer's disease. It, in particular, leads to placement in long-term care facilities and is associated with rapid cognitive decline or increasing cognitive decline, caregiver burden, increased mortality. It's highly prevalent in individuals with Alzheimer's disease. It's about 70% of individuals with Alzheimer's disease have agitation. We've conducted a full suite of trials of AXS-05 in Alzheimer's disease agitation. We have three positive trials of different trial design.
The results, highly consistent, and both in terms of parallel group and randomized withdrawal design. We see a high impact to efficacy, but also with a tolerability profile that makes sense or is consistent with an elderly patient population. No mortality signal, no fall signal. We like the totality of the data we've generated. As such, we'll be submitting an sNDA for Auvelity in the third quarter of this year. The work here is building the package. As I mentioned, the clinical work is done. It's building, it's compiling, writing, building the package. It's on track for a 3Q submission. We'll keep everyone posted there. The other program that we're working on for AXS-05 is smoking cessation. What we've shared is we'll be starting a phase III trial in this indication later this year.
Solriamfetol, I mentioned that it's approved for excessive daytime sleepiness in two indications. We think the product, this is based on KOL feedback, is potentially highly relevant to a number of other indications in CNS. That has to do with its mechanism of action. As I mentioned, it's a DNRI with wake-promoting effects. The indications that we've prioritized for continued development of Solriamfetol are ADHD, major depressive disorder, binge eating disorder, and excessive sleepiness associated with shift work disorder. These are all phase III programs for ADHD and MDD. I'll talk about this. The first trials have been completed. For ADHD, we need to complete two trials, one adult and one pediatric adolescent trial. The adult trial, we announced the results of the FOCUS trial earlier this year. Positive study results are here.
The next step for this program is initiating the pediatric trial, which we expect to do later this year. Major depressive disorder, we were very interested in Solriamfetol in MDD, again, from a mechanistic perspective. We launched a proof-of-concept trial to explore its potential activity in the indication and in specific subgroups. The key subgroup of interest was individuals with major depressive disorder who also have excessive daytime sleepiness. That is about half of patients with MDD. What we had from a pre-specified subgroup analysis is that we saw a signal in that group. The continued development for that program will be to launch another phase III trial in patients with MDD with EDS. Stay tuned for updates there. As I mentioned, binge eating disorder, it is in a phase III trial right now. We will, which is shown here.
This is the ENGAGE phase III trial. This trial is ongoing, and we expect top-line results next year. The final program for Solriamfetol is shift work disorder or excessive sleepiness with shift work disorder, highly prevalent. A key area of focus for us, especially given the product is wake-promoting and is already approved for excessive sleepiness and related indications. The trial that's ongoing is the SUSTAIN phase III trial. We expect top-line results next year. Okay, reboxetine, this is our AXS-12 product candidate for narcolepsy. Clinical program has been completed, and we have three positive trials, also of different design, so parallel group and randomized withdrawal that will comprise or form the basis of the new drug application that we plan to submit in the second half of this year. The focus will be Cataplexy in patients with narcolepsy.
However, we did show a signal in a number of associated symptoms, sleepiness, cognition. We'll have more to say as that package is built, but it's on track for the second half of this year. AXS-14, esreboxetine. This is the S and the anti-emer of reboxetine. The package here, just being mindful of time, is that we have two trials conducted, both positive in pain and Fibromyalgia. There are key other endpoints that we looked at with respect to a potential product differentiation, in particular with respect to fatigue. These studies comprise the basis of our NDA, which we have submitted to FDA and are waiting for a potential acceptance decision from FDA in the second quarter, which, of course, would be this month. Stay tuned there.
All of these programs, they're backed and supported by a very strong IP portfolio and other proprietary technologies with respect to, say, drug substance or drug product. AXS-12, of course, also has orphan drug designation. Company is well funded to reach cash flow positivity based on the cash on hand now. The current operating plan factors in all of the development work and launch work that I've discussed. Cash flow positivity is in sight on the horizon, probably even closer than on the horizon. We have not provided guidance to when we expect that to occur, but very comfortable with achieving cash flow positivity. We're very pleased with the current financial foundation for the company. Got a very strong board of directors and leadership team. I'll conclude with that.
Of course, it's been a busy year so far, and there's a lot to come. Myles, I don't know if just in the time you have or we have that if you want to cover anything. Thank you all.
Thanks, Mark. Appreciate it. We do have a lot of things here. I can open it up for questions, but I also control the volume of my voice. My first question is, when are you launching SYMBRAV O?
I wasn't sure if I covered that enough, so.
No, my first question is actually the range of peak sales for Auvelity that you've given in MDD, $1 billion-$3 billion, quite wide goalpost there, but attractive nonetheless. Can you just kind of walk us through what are the considerations for the bottom end of that peak sales estimate?
Sure.
You're already at $400 million, and what's at the top end?
Sure. We may refine that and hone in on that number over time, but we feel very, very comfortable with the floor just based on the current run rate and the current underlying demand, which is $400 million as of Q1 and the growth that we continue to see. Exactly where we think we'll end up is it's going to be the confluence of continued evolution on the market access side, just coverage in the commercial and government channels. In the commercial channel and in the government channel, it's essentially 100% of lives are covered. In the commercial channel, it's about 63% of lives. The market access team, their work is well underway, and we expect that to evolve substantially as we approach steady state, excuse me.
What we mean by evolve is the overwhelming majority of lives in the commercial channel will be covered and that we expect utilization management to improve over time. You see with a class of antidepressants it is heterogeneous in terms of GPOs and payers, how they prefer to manage the class. You see different things, but usually it is some combination of preferred unrestricted to, say, PA with some number of steps. We expect that to improve. Depending on to what extent that occurs from a timing perspective, that can affect peak. DTC, how the ROI on those initiatives and field force expansion, if there is continued expansion or steady state, which is what we expect for the time being, that to us, how that manifests in scripts, that would allow us to refine that guidance.
We feel very comfortable with that floor of $1 billion.
Yeah. And then maybe just on sort of gross to net and how that's evolving over time for Auvelity, especially if the anticipation is you pick up additional coverage in the commercial channel, any sort of commentary on how that's evolving or what that number is?
Yeah. In the first quarter, we saw it in mid-50s. We expect that number to carry forward for the time being. In steady state, we expect to be in the 50s. We do expect flux, say, intra-year or quarter to quarter, just because you also have, you have the dynamics of additional coverage coming online or, say, rebating that will occur with payers and that is ever evolving. You have the kind of annual or seasonality aspects that lay on top of that. We expect that to continue to steady state, there to be some ebbing and flowing, but in the near term, we expect it to be mid-50s.
Is there anything that the results know exactly what surrounding drugs?
Sure.
Is it approved for the acute treatment?
Sure. It is approved for the acute treatment. That is when you have an attack, aborting that specific attack. One thing that is interesting, though, just with respect to migraine, is frequent attacks and inadequately treated attacks lead to the chronification of migraine. If you can interrupt that cascade, both intra-migraine cascade, but then also chronification, that could be very interesting. Of course, we have long-term treatment data from our studies, but we will monitor how the product is used in the real world to maybe have insights to the broader question. The way the product is, that is one of our multi-mechanistic products. Both are very rapid acting where you want to, the idea is to interrupt the migraine cascade in two different places. One of the components has a very extended half-life.
The rapid acting nature of this utilizes our mosaic technology, which is a formulation technology that dramatically reduces the Tmax of meloxicam in particular. It also speeds up the other component, rizatriptan, as it so turns out. Meloxicam has an extended half-life. The half-life is 20 plus hours. You want to abort the migraine cascade, but then also have durable pain relief. When I mentioned in the beginning that we have or we generated data in a variety of migraine severities, we saw the same thing in terms of two-hour pain relief, but then also 24, 48-hour pain relief.
Maybe just while we're on SYMBRAVO, just you've generated a wealth of evidence in multiple different types of migraine patients. What's the initial sort of target patient profile that you're going to be launching SYMBRAVO in this month?
Sure. Miles is correct. The clinical data that we generated was, say, in mild migraine to individuals with migraine with inadequate response to prior oral treatment. That can be any prior treatment or specifically prior treatment with oral CGRPs. We saw the same thing in terms of durable efficacy. The feedback we've received from KOLs is that they could see using it in a number of settings. Say, after a triptan, which is the baseline of how payers manage the class, to even after in a patient who's received multiple oral treatments for migraine. Say, even after oral CGRPs. It can live anywhere. Our strategy, of course, is you'd like to see it be available from a utilization management perspective for as many appropriate patients as possible. In the early days of launch, HCPs will have optionality.
The patient support programs that we'll have in place at launch will facilitate clinicians, HCPs being able to write the product for the patient profile that they deem appropriate. That's one thing that we're really excited about, the data we have. It's in different types of patients. Ultimately, steady state, it will be the confluence of real-world utilization and then utilization management.
Cool. We're pushing up on time here. The breakout session will be in Burnham A upstairs. Help me in thanking Mark and also Ashley and the crowd here from Axsome Therapeutics.
Thanks, Miles.