Axsome Therapeutics at 45th Annual William Blair Growth Stock Conference: Strategic Insights

On Tuesday, 03 June 2025, Axsome Therapeutics (NASDAQ:AXSM) presented at the 45th Annual William Blair Growth Stock Conference. The discussion, led by COO Mark Jacobson, provided a strategic overview of the company’s current status, commercial progress, and future development plans. While the company is well-positioned financially, with promising product pipelines, the focus on innovation and market expansion also presents challenges in execution and competition.

Key Takeaways

• Axsome Therapeutics is focused on CNS treatments, with three commercial products and more in development.
• The company anticipates seven new products or indications by 2027, aiming for cash flow positivity.
• Avelity’s sales are projected to peak between $1 billion and $3 billion.
• Simbravo’s launch for migraines is imminent, targeting a wide range of patient profiles.
• Axsome is expanding its sales force and considering direct-to-consumer strategies.

Financial Results

• Avelity:

- Current annualized run rate: Approximately $400 million

- Projected peak sales: $1 billion to $3 billion

- Gross-to-net: Mid-50s percentage expected near term

• Sunosi:

- Current annualized run rate: Approximately $100 million

• Overall Financial Position:

- Well-funded to achieve cash flow positivity

- Potential peak sales of approved products: $2 billion to $4.5 billion

- Potential peak sales of the entire pipeline: $16.5 billion

Operational Updates

• Avelity:

- Sales team expanded to 300 account managers

- Preparing for potential national DTC effort

• Simbravo:

- Launch expected this month

- Targeting various migraine severities

• Pipeline:

- NDA submission for AXS-14 in fibromyalgia expected in Q2

- sNDA submission for AXS-5 in Alzheimer’s disease agitation targeted for Q3

- NDA submission for AXS-12 in narcolepsy targeted for second half of the year

- Phase 3 trials ongoing for salriamfetol in binge eating disorder and shift work disorder

Future Outlook

• Product Pipeline:

- Expects seven potential new products or indications by 2027

• Label Expansion:

- Pursuing label expansion for Sunosi

• Clinical Trials:

- Initiating a pediatric trial for salriamfetol in ADHD

- Starting a Phase 3 trial for AXS-5 in smoking cessation

Q&A Highlights

• Avelity Peak Sales:

- Influenced by market access, DTC initiatives, and field force expansion

- Comfortable with a floor of $1 billion based on current run rate

• Simbravo Target Patient:

- Targeting patients with mild migraines to those with inadequate response to prior treatments

In conclusion, Axsome Therapeutics is on a promising path with its innovative treatments and strategic market approaches. For more detailed insights, refer to the full transcript.

Full transcript - 45th Annual William Blair Growth Stock Conference:

Miles Minto, Senior Biotech Analyst, William Blair: To the the William Blair forty fifth Annual Growth Stock Conference. My name is Miles Minto. I’m a senior biotech analyst here at the firm. I cover the neurosciences and genetic medicines, and Axsome has been a day one coverage company for me. So early two thousand seventeen before before the Ascend data actually was when picked up coverage there.

You know, obviously a bona fide growth story with a Vality well underway, launch of a novel antidepressant here, and Sunosi really coming into its own as well. So 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. So 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. So thanks very much. I will say before Mark gets started, important disclosures are available at williamblair.com.

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Develop and deliver innovative transformative medicines for the millions of people, the hundreds of millions of people in The US and globally who are living impacted living with or impacted by CNS conditions. And we think about that in in a few different ways. We think about, in particular, delivering innovative treatments for areas of unmet need. And 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 and there’s only one product currently approved to other indications where there are are multiple products approved such as migraine. However, patient outcomes are are are lacking or or not where they should be or there’s been little innovation.

So we think about our we’ll run through the pipeline and portfolio, but we think about CNS as two broad categories, psychiatry and neurology. And we have a deep and broad pipeline within each category. So psychiatry, depression, Alzheimer’s disease agitation, ADHD, binge eating disorder, smoking cessation. And then neurology, obstructive sleep apnea, migraine, narcolepsy, fibromyalgia, and shift work disorder. And we’ll touch on this, but there there’s high overlap between a a number of these indications and and, hence, the the platform that we’re building on the r and d side and also the commercial side.

So all in all, these indications, they they they they impact over a 50,000,000 lives in in The US. And the way we think about impacting these indications are there are five pillars of innovation, the way we think about it. First, novel or first in class mechanisms of action. So different differentiated treatment options at the mechanistic level. And then we also think about the confluence of multiple mechanisms simultaneously for an indication.

And we’ll get into the specifics here. And one area in particular that that we focus on is metabolic pharmacokinetic modulation. And that is, right, using the body to modulate its own metabolism of API’s drug substances to elicit differentiated pharmacodynamic outcomes. Clinical trial innovation, psychiatry in particular, very difficult to detect treatment differences. And high, high rates of placebo response.

We also innovate on clinical trial design and experimentation design to allow us to detect treatment signals, or to to give our to give ourselves a better shot at it. And then we also have a a molecular innovation with respect to drug delivery. Where is the company today? You know, Miles mentioned that the company is in a dramatically different place from from when he, started following the recovery. The the company when he initiated in in 2017 is is much, much different.

So, we have three commercial programs now, two of which we developed from scratch in house. So, idea was born at Axsome, took it through the clinical and regulatory stages and and are one of which is launched. That’s Evality for major depressive disorder. And the other is launching this month or will become commercially available. That is Simbravo for migraine.

We have three NDA stage programs. We’ll talk about those. Four programs addition to the NDA stage programs and ongoing phase three clinical development. And taken together, that positions us to have seven potential new products or new indications to the existing products by 2027. So just just a a fantastic time for the company, highly diversified in in all aspects of the business and and currently in a phase of of high growth.

Here’s the pipeline, and again we break it into psychiatry and neurology. And I will run through the different programs and I’ll try and touch on all those today with the time that we have. But, you know, in totality, we think this is a singular pipeline with respect to CNS in the industry. And, know, 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 and a half billion dollars.

And and if you look at just the products that are approved today, so Ovelity, Sunosi, Simbravo, potential peak of 2 to 4 and a half billion dollars. So just just a fantastic potential for the company. And, again, it’s it’s a very exciting time for us. So so if we deliver innovation to patients and we do that in a sound business fashion, we’ll we’ll deliver high returns to shareholders. Twenty twenty five, already, it feels like we’ve we’ve already had a full year under our belt and so for the company and and and macro as well.

But just to look at what we’ve done so far this year, Symbravo was approved at the start of the year, the January, and we’ve had a number of clinical phase three trial readouts which were positive. So we had the EMERGE phase three trial of Symbravo. That’s an oral CGRP non responders. That was a positive study. We had two Phase III trials for salriamfetol.

One is the FOCUS Phase III trial in ADHD, adult ADHD. That study was positive. I’ll talk about next steps. Then we had a proof of concept trial we call the PARADIGN trial of Saoriamfetol in major depressive disorder. I’ll talk about that as well.

But the results there facilitate continued development in that indication. And then the balance of 2025 and beyond, we have the launch of Sunbravo. I touched on that. We expect that to be this month. Then the three NDA stage programs we expect in in in first half, so so soon, to hear from FDA on a filing acceptance decision.

So that that’s an acceptance decision with respect to our NDA submission of AXS-fourteen in fibromyalgia. And then we are on track for the sNDA for AXS-five in Alzheimer’s disease agitation for a 3Q submission and then an NDA submission of AXS-twelve in narcolepsy. Ongoing phase three trials of salriamfetol in binge eating disorder and excessive sleepiness associated with shift work disorder. Those are moving along. Enrollment’s continuing, and we expect results next year.

And then we’ll be starting a number of trials this year as well, a number of phase three trials, and I’ll cover that. So, commercial side of the business, three three products. Ovelity, that’s our our product for major depressive disorder. That is one of the two, as I mentioned, that that we developed in house and and took through approval and launch. High growth right now.

It’s 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. And that is the product approved for excessive daytime sleepiness in narcolepsy and OSA. Then we have some Bravo, which is approved for the acute treatment of migraine in adults with or without aura. And again, just one more time, that will be launching, we expect, this month. AVELITY.

So it’s a rapid acting oral NMDA receptor antagonist. We have some some callouts of of the data that were generated and and the product profile and and what is it. It’s It’s fast and it lasts. And 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. So HCPs are bringing the product up in the treatment paradigm or treatment algorithm, which which we think is a great sign. And as you can see, the total scripts just high growth at this point in time. And, it’s currently as of q one, you know, annual you know, current run rate annually of of about 400,000,000. So it’s well on the way to our our target peak sales of of 1 to 3,000,000,000 in MDD.

And one thing I will touch on is just some potential drivers for continued growth. So in the first quarter, we expanded the sales team to 300 account managers. It was at about two sixty, so we added about 40 additional more. That allows us to go further into primary care. And we’d expect so we’re we’re starting to see impact in terms of new to brand scripts.

We expect that to continue through the balance of the year. And then other drivers are continued improvements and evolution in market access and in coverage in the commercial channel. And then we are also preparing for a potential national DTC effort. That that would be you know, if that’s something we would do, it would be the second half of this year or thereafter. And so the team is monitoring the market right now, and we’ll we’ll make a decision, a deployment decision, and we’ll keep everyone posted on that.

Sunosi, as a first and only dopamine and norepinephrine reuptake inhibitor approved for excessive daytime sleepiness in narcolepsy and OSA, and 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, and and we see that here especially with a very a very healthy business. The the field force, I’ll just comment on that because I the field force here, it’s it’s a smaller field force there, and it’s it’s about 75 account managers. And I’ll I’ll comment on on the Sun Bravo field force as well.

But current status quo is is, you know, steady growth, and I will talk about the efforts on the development side for potential label expansion for Sunosi. And you can see annualizing it at about a hundred million dollar run rate. So we’re pleased with that. Simbravo, one more time for good measure. We’ll be launching that, we expect, this month.

And what’s important here with respect to the product profile is, the efficacy that was demonstrated in the clinical development program. So that was across a variety of migraine severities. That’s very important. Mild, moderate, and severe. And we saw robust responses in in terms of pain freedom, sustained pain freedom, freedom from most bothersome symptom, and ability to return to normal functioning.

And we’re we’re excited to launch that. Launch ready Launch prep is, you know, it’s it’s essentially, you know, t minus just just a few weeks here, and stay tuned for the formal update. But the migraine, there are a number of, obviously there are a number of products approved, but overwhelmingly, eighty percent of patients are highly dissatisfied with treatment options now that 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. So that’s the quick summary of the commercial side of the house.

Turning to the development side, first and foremost, AXS-five for Alzheimer’s disease agitation. This program is something that we’ve been working on for a number of years I’ll touch on that. But Alzheimer’s disease agitation is one of the critical symptoms of Alzheimer’s disease. And 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, and it’s highly prevalent in individuals with Alzheimer’s disease.

So it’s about seventy percent of individuals with Alzheimer’s disease have agitation. So we’ve conducted a full suite of trials of AXS-five in Alzheimer’s disease agitation, and we have three positive trials of different trial design and 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. So no mortality signal, no fall signal, and so we like the totality of the data we’ve generated. And as such, we’ll be submitting an sNDA for Ovality, in the third quarter of this year.

And the work here is building the package. So, you know, as I mentioned, clinical work is done. And so it’s building. It’s compiling, writing, building the package, and it’s on track for a 3q submission. We’ll keep everyone posted there.

The other program that we’re working on for AXS-five is smoking cessation. And what we’ve shared is we’ll be starting a phase three 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 in CNS, and that that has to do with with its mechanism of action. As I mentioned, it’s a DNRI with wake promoting effects.

And so, the indications that we’ve prioritized for continued development of salriamfetol, ADHD, major depressive disorder, binge eating disorder, and excessive sleepiness associated with shift work disorder. And these are all phase three programs for ADHD and MDD. I’ll talk about this. The first trials have been completed for ADHD. We need to complete two trials, and one adult and one pediatric adolescent trial, adult trial.

We announced the results of the FOCUS trial earlier this year. Positive study, results are here. And 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 sauramfetol in MDD, again from a mechanistic perspective, and we launched a proof of concept trial to explore its potential activity in the indication and in specific subgroups.

And the key subgroup of interest was individuals with major depressive disorder who also have excessive daytime sleepiness. That’s about half of patients with MDD. And what we had from a pre specified subgroup analysis is that we saw signal in that group, and so the continued development for that program will be to launch another phase three trial, in patients with MDD with EDS. So stay tuned for updates there. And as I mentioned, binge eating disorder, is in a phase three trial right now, which is shown here.

This is the ENGAGE phase three trial. This trial is ongoing and we expect top line results next year. Then the final program for solriamfetol is shift work disorder or excessive sleepiness with shift work disorder. Highly prevalent and, a key area of focus for us, especially given the product is wake promoting and is already approved for excessive sleepiness and related indications. And the trial that’s ongoing is the SUSEIN phase three trial, and we expect top line results next year.

Okay, riboxetine. This is our AXS-twelve 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. And so the focus will be cataplexy in patients with narcolepsy, however, we did show a signal in a number of associated symptoms, sleepiness, cognition, and we’ll have more to

Miles Minto, Senior Biotech Analyst, William Blair: say

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: as that package is built, but it’s on track for second half of this year. AXS-fourteen, S. Riboxetine. This is the S enantiomer of riboxetine. So the package here, just being mindful of time, is that we have two trials conducted, both positive in pain and fibromyalgia.

Other there were key other endpoints that we looked at with respect to potential product differentiation, in particular with respect to fatigue. And 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. So stay tuned there. And all of these programs, they’re 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-twelve, of course, also has orphan drug designation.

The company is well funded to reach cash flow positivity based on the cash on hand now, and the current operating plan factors in all of the the development work and and launch work that I’ve that I’ve discussed. So cash flow positivity is 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. So we’re very pleased with the current financial foundation for the company. Got a very strong board of directors and leadership team, and, you know, I’ll I’ll conclude with that.

But, of course, it’s been a busy year so far, and and there’s a lot to come. And, Miles, I don’t know if just in in the time you have or we have that if you wanna cover anything. But thank you all.

Miles Minto, Senior Biotech Analyst, William Blair: Thanks, Mark. Appreciate it. Can open it up for questions and also control the volume of my voice. But my my first question is when are you launching Simbravo?

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: I wasn’t sure if I I covered that enough.

Miles Minto, Senior Biotech Analyst, William Blair: My question is actually the range of peak sales for Avelity that you’ve given in MDD, one billion to $3,000,000,000 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?

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Sure.

Miles Minto, Senior Biotech Analyst, William Blair: Or are you at $400,000,000 and what’s at the top end?

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Sure. The we’ll we may refine that and hone in on that number over time, but we we feel very, very comfortable with the floor just based on the current run rate and the current underlying demand, which 400,000,000 as of as of q one, and the growth that we continue to see. And exactly where we think we’ll we’ll end up is it’s gonna be the confluence of, you know, continued evolution on on the market access side, so just just coverage in the commercial and government channels. So in commercial channel and in the government channel, it’s it’s essentially a % of lives are covered. In the commercial channel, it’s about 63 of lives.

So, the market access team, their their work is well underway, and we expect that to evolve substantially as we approach steady state. Excuse me. And what we mean by evolve is is, you know, overwhelming majority of lives in the commercial channel will be covered and that we expect utilization management to improve over time. So what you see with a class of antidepressants is heterogeneous in terms of GPOs and payers, how they prefer to manage the class. So you see different things, but usually it’s some combination of preferred unrestricted to, say, PA with some number of steps.

So we expect that to improve. And depending on to what extent that occurs from a timing perspective, that can affect peak and then DTC, how that the ROI on those initiatives and and field force expansion if there’s continued expansion or, you know, 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 guidance. But we feel very comfortable with that floor of 1,000,000,000.

Miles Minto, Senior Biotech Analyst, William Blair: Then maybe just on sort of gross to net and how that’s evolving over time for Evality, 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?

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Yeah. So in the first quarter, we saw it in mid-50s, and we expect that number to carry forward for the time being. In steady state, we expect to be in the fifties. And we we do expect flux, say, intra year or quarter to quarter just because you also have so you have the dynamics of additional coverage coming online or, say, rebating that will occur with payers and that is ever evolving. And then you have the kind of annual or seasonality aspects that lay on top of that.

So we’d expect that to continue to steady state. There to be some, you know, ebbing and flowing, but in the near term, we expect it to be mid fifties.

Miles Minto, Senior Biotech Analyst, William Blair: So and Mhmm.

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Sure. Sure. So it is approved for the acute treatment. So that is when you have an attack aborting that specific attack. One thing that is interesting though and just with respect to migraine is frequent attacks and under inadequately treated attacks lead to the chronification of migraine.

So if you can interrupt that that cascade, both intramigraine cascade but then also quantification, that could be very interesting. And, of course, we have have long term treatment data from our studies, but we’ll we’ll monitor how the product is used in the real world to, maybe have insights to to the broader question. But the way the the the product is, so that is that that is one of our multi mechanistic products and both are are very rapid acting where you want to, the idea is to interrupt the migraine cascade in in two different places, but then one of one of the components has a very extended half life. And the rapid acting nature of this utilizes our mosaic technology, which is a formulation technology that dramatically reduces the t max of meloxicam in particular. It also speeds up the other component, rizatriptan, as it so turns out.

But meloxicam has an extended half life. The half life is twenty plus hours. And so you want to abort the migraine cascade but then also have durable pain relief. And 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 twenty four, forty eight hour pain relief.

Miles Minto, Senior Biotech Analyst, William Blair: Maybe just while we’re on Simbravo, you’ve generated a wealth of evidence in multiple different types of migraineur patients. What’s the initial sort of target patient profile that you’re going to be launching Simbravo in this month?

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Sure. So 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. You know, that can be any prior treatment or specifically prior treatment with oral CGRPs. And we, you know, we saw we saw the same thing in terms of in terms of durable efficacy.

And when you the feedback we’ve received from KOLs is that they they could see using it in a number of settings. So, say after a triptan, which is how you know, the baseline of how payers manage the class, to even after in a patient who’s who’s received multiple oral treatments for migraine, so say even after oral CGRPs. And so 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. But in the early days of launch, you know, HCPs have option will have optionality and and the the patient support programs that we’ll that we’ll have in place at launch will will facilitate clinicians, HCPs being able to write the product for the patient profile that they deem appropriate.

But that’s one thing that we’re really excited about the data we have. It’s in different types of patients and then ultimately steady state it will be the confluence of real world utilization and then utilization management.

Miles Minto, Senior Biotech Analyst, William Blair: Cool. We’re pushing up on time here. So the breakout session will be in Burnham A Upstairs. Help me in thanking Mark and also Ashley in the crowd here from Axon Therapeutics.

Mark Jacobson, Chief Operating Officer, Axsome Therapeutics: Thanks Myles.

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