All right, I think in the interest of time, we'll get started here. Welcome back to the William Blair Growth Stock Conference. It's the 44th edition this year in 2024. My name is Myles Minter. I'm a senior biotech analyst here at the firm. I cover the neurosciences and genetic medicines, and importantly, today, I do also cover Axsome Therapeutics. For full disclosure and relevant commentary on that, please see williamblair.com. It is my pleasure to have with us today the Chief Executive Officer and founder of the company, Herriot Tabuteau. So thanks very much. He's coming from New York, and also in the room here, we have Mark Jacobson, the Chief Operating Officer as well. So, if you have any questions after the presentation, we'd be happy to field them.
Very, very quickly, Axsome obviously launching a novel antidepressant currently that is called Auvelity. You know, I think that this has been a very successful early drug launch and looks really promising, not only for patients, but obviously for the top line growth for the company as well. Did $130 million in its first full year of launch or thereabouts, and it's on a really nice growth trajectory since then. But there's potential for it to be expanded into Alzheimer's disease agitation as well, which is a substantial market opportunity. I also think that the rest of the pipeline, which Herriot might comment on today, is undervalued and underappreciated as well. So that's enough of me talking. I'll pass it over to Herriot.
All right. Thanks, Myles. Thank you for having us present at your conference. I will be making forward-looking statements, so I do urge you to read our SEC filings for a full description of the risks and uncertainties associated with our business. Axsome is a commercial stage biotech company that's focused on neuroscience, and we also have a broad and deep late-stage pipeline. We have two marketed products, and these are Auvelity for the treatment of major depressive disorder and Sunosi for the treatment of excessive daytime sleepiness. On the back of that, we have five product candidates that are in development across 10 different indications. These indications are serious neuropsychiatric indications that affect roughly 150 million patients in the U.S. alone.
So that's a lot of inspiration for our team to continue to work hard to bring new treatments to patients with these disorders. Now, given the late-stage nature of our pipeline, what that means is that we're very close to bringing a lot of treatments to market in a very short period of time. So in addition to Sunosi and Auvelity, we have the potential to bring to market AXS-12, AXS-07, AXS-14, and AXS-05 in Alzheimer's disease agitation, all by 2025. So that would be potentially six marketed product candidates or indications by 2025. So what I'd like to do now is give you a status of our currently marketed products, and after that, I'd like to provide you a status on the pipeline. So starting with Auvelity.
This is our first-in-class novel oral NMDA receptor antagonist, which is being marketed for the treatment of depression. We're pleased with the strong launch of Auvelity to date, and feedback from HCPs highlight that the product profile that they're seeing in the clinic is consistent with the label. HCPs focus their comments on the rapid onset of action of Auvelity, the large magnitude of treatment effect, as well as the favorable tolerability profile. Prescriptions are showing robust quarter-over-quarter growth, and we are starting to see the impact of our recently upsized field force. Now, we continue to make progress to broaden patient access, and we recently signed on, on that front, a second group purchasing organization. Sunosi is our second marketed product candidate...
Well, our second in-market, our second marketed product, and this is a first-in-class dopamine and norepinephrine reuptake inhibitor, as well as a TAAR1 receptor agonist. So growth in the current indication has been very steady. We believe that Sunosi has significant, significant potential, not just in the current indication, but also in the future indications, which we will discuss later. I'd like to now turn to our development pipeline, starting with AXS-05, the active molecule in Auvelity. We are developing AXS-05 for Alzheimer's disease agitation. There are close to seven million patients in the U.S. who suffer from Alzheimer's disease, and approximately 70% of them also suffer from agitation. This is an area of high unmet medical need, with only currently one product that is approved to treat this indication.
We have completed two phase 3 trials in Alzheimer's disease agitation, the ADVANCE 1 trial and the ACCORD 1 trial, both of which were positive. We are currently conducting two additional phase 3 trials, the ADVANCE 2 trial and the ACCORD 2 trial, and those two studies do mimic to a large extent the design of their predecessor studies. This is the design of the ADVANCE 2 trial. This is a parallel group study. Enrollment is progressing, and we are on track to announce top-line results for this trial with its completion in H2 of 2024. The ACCORD 2 trial is also a phase 3 trial. The difference is that this is a randomized withdrawal design, so this mimics largely the design of the ACCORD 1 trial.
So enrollment for that study is progressing, and we expect to complete enrollment in the middle of this year. Our next product candidate is AXS-07, and this is our multi-mechanistic treatment for migraine. This is a very large patient population, as most of you are aware of. However, there's still a large need for drugs that work better, that have greater efficacy. And the active ingredients in AXS-07 target the multiple pathophysiologic processes that are associated with migraine. So we have now completed three clinical trials with AXS-07, which demonstrate its treatment effect. We did file an NDA for AXS-07. We received a complete response letter, which was focused on chemistry and manufacturing. We believe that we have addressed those points in the CRL and are getting ready to resubmit our NDA, and we're on track to do that this quarter.
Our next product candidate is, AXS-12. This is reboxetine for the treatment of narcolepsy. So narcolepsy is a large orphan indication and an area of still high unmet medical need. So despite the availability of some treatment options, a lot of those treatment options do have drawbacks which limit the potential patient population. We recently announced positive phase 3 trial results with AXS-12 in narcolepsy, and what we saw in that study was a rapid improvement in cataplexy symptoms. We also saw a rapid improvement in the severity of excessive daytime sleepiness, as well as an improvement in cognition. We are currently conducting an open-label safety extension trial with AXS-12, which we expect to complete by the end of this year, and upon completion of that, we will be positioned to start preparing the NDA for this product.
Our next product candidate is the AXS-14. Now, this is the S-enantiomer of reboxetine, which is being developed to treat fibromyalgia. This is a very prevalent condition. So there are five million patients in the U.S. who currently have fibromyalgia, 90% of whom are women, and there are currently only three products approved to treat fibromyalgia. So, very limited treatment options and a great opportunity for a product like AXS-14, which has the potential to deliver significant efficacy. And I say that based upon the results of our phase 3 and phase 2 studies, both of which demonstrated a rapid and large treatment effect with regards to pain, and also an improvement in function, which were highly statistically significant.
So currently, we are in the final stages of preparing our NDA submission for AXS-14 for this indication, and we expect to do that in the second half of 2024. So moving on to our next product candidate, which is solriamfetol. Solriamfetol is the active molecule in Sunosi. Now, solriamfetol is a dopamine and norepinephrine reuptake inhibitor. It is also a TAAR1 receptor agonist. So this is a new mechanism of action, and we think that based on this pharmacology, that there is the potential to address a number of different neuropsychiatric conditions.
So, the first indication that, the first new indication that we're developing solriamfetol for is ADHD, which affects 17 million patients in the U.S. alone, and, there is still a need for drugs, that have a high level of efficacy, so, in other words, a high treatment effect, but also drugs which, don't have the limitations of the current stimulant medications. So we are currently in a phase three trial, the FOCUS trial of, solriamfetol in ADHD. That study is, enrolling well, and we expect to have top-line data in the second half of this year for, solriamfetol in this indication. We also developing solriamfetol to treat major depressive disorder.
This is a large patient population, and given the heterogeneous nature of this disease, we believe that drugs that have novel mechanisms of action, like Auvelity, for example, which we currently are marketing, as well as Sunosi or solriamfetol, which has the unique TAAR1 mechanism of action, we believe that those treatments will be welcome additions to the armamentarium of psychiatrists and other healthcare professionals who take care of these patients. We are currently conducting a phase 3 trial in this indication, which we recently launched. This is the design of that study, and we are on track to deliver top-line results from solriamfetol in the PARADIGM trial in 2025. We're also developing solriamfetol for the treatment of, for the treatment of binge eating disorder or BED.
So BED is the most common eating disorder, and it affects seven million patients in the U.S. alone. We recently launched the ENGAGE phase III trial, and we expect to have results from that study in 2025. The last indication that I'll talk about with regards to solriamfetol is shift work disorder, specifically excessive daytime sleepiness in patients who suffer from shift work disorder. This is a large patient population. There are approximately 15 million patients in the U.S. who conduct shift work. This is the design of that study, and we expect to start that trial in this quarter, actually. Great. So all in all, we have a very broad, deep, and late-stage CNS pipeline, which has the potential to generate total U.S. peak sales of up to $16.5 billion. Our...
All the work that we're doing is protected by a very strong intellectual property portfolio, and this allows us to make the investments that are needed to bring these novel treatments to market and to make sure that we deliver value for patients as well as shareholders. We ended the quarter with $331 million in cash, and this provides us a runway to reach cash flow positivity without any additional capital raise. We have a very talented management team and also a very strong board of directors. So this is gonna be a very busy period for Axsome, okay? So we expect the balance of the year to be highly productive, with numerous milestones, regulatory and commercial milestones.
These include NDA submissions, as well as top-line results from several pivotal trials, as well as making progress on some of the other studies which will be ongoing. Okay. Now, all of this will exemplify, hopefully, what the Axsome team goes into the office every day to do, which is to develop treatments for patients who suffer from serious neurological and psychiatric conditions. So I, I'm excited every year about the work ahead, but I'm especially excited about the work ahead over the next 12-18 months because it will lead to a lot of revelations with regards to how our products work and a lot of potentially value-driving milestones. So I look forward to keeping you updated over the balance of the year and into next year. Thank you.
Cool, cool. I think we've got 14 minutes left at the moment, so I can kick off some Q&A if anyone in the audience would like to chime in as well. I'm happy to take questions, but you, you did lay out the peak sales estimate for Auvelity there in between $1 -3 billion. You know, I made mention in the first year, you're at about $130 million in revenues here. So you know, two questions: What, what sort of, like, puts the bookend of the $1 billion-
Mm-hmm
... to $3 billion peak sales estimate there, and I guess, like, any sort of guidance as to, like, the length of time that you're projecting that you'll get within that range?
Sure. So the reason for the bookmark is it's really driven by the size of the market for depression. This is a very large market, you know, 21 million patients in the U.S. with MDD, and also the high unmet need. So approximately two-thirds of patients fail first-line treatment with SSRIs and SNRIs. So when you think about the market, any small movement whatsoever in terms of penetration, and it only needs to be very small, leads to very large numbers. So that's the reason for it. It's really to lay out what the possibilities are. I think, you know, another question is where will it be used in treatment?
So, I think that initially, when there is a new product that is launched, the idea is that it will be used for later lines of treatment, and, you know, obviously, if it's used for earlier lines of treatment, that adds to the upside potential. The question is, you know, is the product appropriate to be used in earlier lines of treatment? And a lot of that really depends on the clinical experience, so the experience that clinicians see when they give the drug to patients, in terms of its tolerability, does it work well enough? And, what we've been watching, of course, is the lines of treatment that Auvelity is being slotted into.
If you go back to the fall or the end of 2023, roughly 40% of the prescriptions were being written for first- and second-line treatment, and as of the latest quarter, that has increased to about 50%. So we think that bodes well for the trajectory of the product. And you mentioned that last year it did about $130 million in sales. So the current run rate is about $200 million in sales. So we're definitely heading in the right direction, and it's something that we just need to continue to watch in terms of its adoption.
You also mentioned that you've, you know, brought on an expanded sales force effort as well. I guess, when should we expect a pull-through, particularly on the total script counts that you showed us as well? Is that gonna happen, you know, throughout this year? Is it gonna be back-weighted through this year, or is it more a 2025 thing that we're looking at here? What's the sort of trajectory and your expectations of that sales force?
So the sales force expansion concluded, in other words, everybody was on board, at the very end of 2023, and they became, they started to become productive in the first quarter. So we are definitely seeing their contributions now, and, and we think that, that we are seeing that, and we will continue to see that in the second quarter. And then we would expect, as they gain experience, for their productivity to only increase.
And then, a common question that I get from investors is the access to Auvelity. And you mentioned you are seeing usage like up the lines of therapy, but it's more like what sort of reimbursement channels these patients are coming through. And I think a lot of people point to your commercial covered lives access, which I think is at 48%. You know, how do we sort of, you know, improve on that? If we do improve access, does that come at a detriment to gross to net discounting? And, you know, I guess, what sort of like near-term benefit can we see in that access number from 48%? Where do you want to get to?
Well, if you take Sunosi, for example, as a proxy, the covered lives is about 86%, total overall, and currently, we are at 70%. So, so that's 48%, 48%-50% commercial lives, and 100% in the government channel. So the overall mix is 70%. So we fully expect that that is going to increase and improve over time. And in terms of, you know, what impact there could be on gross to net with improvement in coverage, you know, what I will say is that we're very disciplined in terms of our in terms of the contracts that we do sign.
So we did announce that we signed a contract with a second large group purchasing organization in the quarter. So the way to think about the group purchasing organizations is that there are three large ones, and each one controls about one-third of the commercial covered lives. So we wanna make sure that we get access for the drug for as many patients as possible. That is key, but we also wanna make sure that we're disciplined from a commercial perspective and from an economic perspective. We think we can accomplish those two objectives and make sure that we have a gross to net, which is something that you would expect for a company in our space at maturity.
Maybe just on, like, formulary positioning, and as we try and get up the lines of therapy here, I mean, that sort of remaining... The 50% of scripts that you're not seeing frontline and second line or below there, are they coming from plans that have maybe, like, less favorable formulary positioning, and that's why they're in second line? Or is that just a clinician choice or a patient choice to use it later?
Yeah. Yeah, we certainly can get at the answer to that. I don't have the granular answer, but it could be... It is likely a combination of all of those factors which you mentioned. There are plans, for example, which have, you know, no step edits whatsoever, and so clinicians are then free to prescribe the product the way that they believe is most fit to prescribe the product. And then, you know, there are also plans where there are step edits. And then also, you do have the patient.
The patient, there are patients who actually have gone through multiple lines of treatment or one line of treatment, and so who naturally would be eligible anyway for Auvelity, regardless of how it's placed in the treatment paradigm at a particular plan.
Maybe switching really quickly to Alzheimer's disease agitation, given the ADVANCE 2 study is gonna read out in the second half, is what you've guided to. You know, we do have a relatively recently approved product there in Rexulti for that indication. Maybe you can comment about the differentiation of AXS-05 for that indication, given you know, we did see recent approval there for Rexulti.
So AXS-05 has a different mechanism of action than the agent that was just approved, which is an atypical antipsychotic. So this is a class of drugs which is available to clinicians. This is a class of drugs which historically has been used off-label to treat patients with Alzheimer's disease agitation. But it is also a class of drugs which per FDA labels mandated FDA labels for all of these drugs which carry an increased risk of mortality in specifically elderly patients with dementia. So it does create a quandary for clinicians to use these agents to treat patients. So now turning to AXS-05, AXS-05 does not fall into that class, so it is different mechanistically.
What we've seen in our clinical trial experience is that AXS-05 works rapidly in patients. It improves symptoms of agitation substantially, and it's also very well-tolerated from our experience. So, you know, we're very excited by the profile and think that it's one that would be welcomed by the geriatricians who take care of these patients.
And then maybe just on, I guess, precise is the wrong way to put it, but what is the path to filing here? What do you need from the trials that you have ongoing, and, you know, do we need open label safety? Do we need manufacturing, anything like that, to actually get this filed in front of the agency? What's the path there?
Yeah. So the path is to complete the studies which are ongoing. And there are three studies that are ongoing. One is the ADVANCE 2 trial, so we do need to complete that study, and that study will provide, very importantly, additional placebo-controlled safety data, which is important. Two is the open label safety extension trial. That's important in order for us to meet ICH guidelines in terms of the numbers of patients needed to be treated in this particular patient population. These are elderly patients with dementia. So, as a reminder, we need to have 300 patients treated for six months and 100 patients treated for one year. So that is a primary goal of the open label safety extension trial.
And then, and then, of course, we would like to have the results of the ACCORD 2 trial. And, so the guidance for completion of enrollment of that trial or reaching the target enrollment is the middle of this year, for that. So, with that, with the completion of those studies, in addition to the prior studies, for which we've announced results, we would be in a position to prepare the NDA.
Maybe we can move on to... I think what doesn't get a lot of coverage is AXS-14 in fibromyalgia. I mean, that this was a drug, I believe you got the rights from some trials done at Pfizer. Can you just comment more on, like, the market opportunity in fibromyalgia? We've had drugs like Cymbalta in there, we've had drugs like Lyrica-
Mm-hmm
... being approved there as well. Just maybe comment on the unmet need there and, you know, the market opportunity, considering that's, like, very new to me in terms of filing and-
Yeah, we're really excited by the fibromyalgia opportunity. It's a large patient population. There are only three drugs, as you mentioned, which have been approved. The efficacy profile of several of these drugs leave a lot to be desired. Then you have AXS-14, which has demonstrated improvement in pain, which is highly statistically significant, improvement in function, which is highly statistically significant. Symptoms, for example, such as fatigue, were adequately treated with AXS-14, and this is a symptom which is very prevalent in patients with fibromyalgia, but which is very difficult to treat. And in fact, some of the current, so of the three available treatments for fibromyalgia, some of them actually make patients more tired.
So, we really like the product profile, and are looking forward to making this drug available to patients. You know, if you go back to, you know, when the clinical trials were being run, when the drug was being developed, and the If you speak to the clinicians who were involved in those studies, and they tell you that the patients were actually saddened, when the studies were stopped because they were getting something from AXS-14, which was not available from the other treatments.
Just the quick final one. To the best of your knowledge, there's no additional clinical work that would be required for that filing?
The additional clinical work was, clinical pharmacology.
Mm-hmm.
And those studies we've been completing.
I see the flashing red screen, so I think we're out of time.
Okay.
Thanks very much for joining us, Herriot.
Thank you.
I really appreciate it.