Thanks, everyone, for joining us. For our next Fireside, we have Axsome represented by their Chief Operating Officer, Mark Jacobson. Thanks for being here.
Thanks a lot, Leo. Really appreciate it. It's been a super productive day for us so far at the conference. I'm happy to answer any questions you may have.
Yeah, great. You know, maybe starting off bigger picture, Axsome's obviously a commercial company. I wanted to talk about some of the macroeconomic impacts just to start off. I guess, what are you seeing in terms of potential impacts to the business from either the manufacturing potential tariffs, either from most favored nation, potential impacts through SUNOSI, or through any IP redomiciling that the administration might try to enforce?
Sure. That is a number of angles. Maybe just a broad observation about the company, which is Axsome is now at a point where it is a highly diversified business commercially, on the regulatory side, and on the development side. The overwhelming bulk of the business, current and anticipated, lies in the U.S. That ties to a number of questions that you have. AUVELITY and SUNOSI are the two products that are on market right now. SYMBRAVO will be launching next month. Two of those, AUVELITY and SYMBRAVO, are commercial only in the U.S. That right away has read-through, or lack of read-through, I should say, with respect to most favored nation, pricing considerations, and things like that. That is good. SUNOSI is available in a few select countries outside the U.S. We think the impact is minimal.
We can talk about that if you'd like to. IP, all of the IP, AUVELITY, SYMBRAVO, all the other programs that Axsome has developed, it's domiciled in the U.S. The exception to that is SUNOSI, which is domiciled in Europe. The reason for that is, as a reminder, we acquired that product. The IP was initially domiciled outside the U.S., so it was kept there. Right now, though, we don't see an impact to SUNOSI with respect to that. Tariffs, we think the impact is immaterial. With respect to, it's a de minimis portion of cost of goods when you model, say, drug substance or drug product manufacturing. We feel good there.
The business is really insulated from a number of these, say, macro factors that are at play, both those of which that are being pulled through and then ones that have been stated as concepts that are being looked at.
Yeah, no, that's great to hear. Obviously, your main commercial product's AUVELITY. It's delivered fairly consistent growth since the launch in 2022. Can you talk about what you expect to see for the balance of the year in terms of demand growth? Where are you seeing the drug being used? How's that evolved since the initial launch?
Sure. So far, product is growing nicely. We are pleased with what we are seeing when you look through different lenses. When you look at how it is being used, patient profiles, about 15% is in first-line use. About 35% is in second-line. It goes from there. That is great. We think that speaks to the differentiated outcomes for patients, both with respect to efficacy, onset of action, rapid acting, durability of effect, and the tolerability profile being distinct from what was previously or what is currently available otherwise. We like that. Another way to think about it or another lens to use is monotherapy. We are already over 50%. I think it is about 55% of the use is monotherapy, which is great when you think about reduction of polypharmacy and things like that for patients. We like that, too.
With respect to outlook and continued growth, we're very pleased with where we are. Currently annualizing about $400 million in sales, which is great. We recently expanded the field force in the first quarter. That completed. We're starting to see an impact in MBRX. We'd expect that impact to continue and to see pull-through into TRX through the balance of the year. We expect to drive continued improvements in market access. That's both the quantity, so the number of lives covered in the commercial channel, which is currently at 63%, and also improvements in quality of coverage. We expect that to also continue to drive growth. The one other approach that we've shared that's in the works potentially for later this year is a national DTC campaign. That's being contemplated.
What we're doing right now is we have some testing that's underway, which would inform a potential national rollout. A lot of opportunity there. It's really just boiling down to patient outcomes, differentiated outcomes. We think that bodes really well for the long-term prospects or opportunity. We've guided to peak sales of $1 billion-$3 billion for AUVELITY in MDD alone.
Got it. You mentioned the DTC campaign. I'm curious how you're thinking about that and with the sales force expansion, how you've sort of targeted them. Are you trying to move more into the primary care market? Are you continuing the push into more of the psych specialists, I guess? Yeah.
Sure. The initial focus of launch and still to this day, but the initial focus was psychiatrists. What we've been doing, we expanded about a year ago in the first quarter of 2024. We expanded with an additional 100 reps. That allows increased reach and frequency. That allowed us to start to go into primary care. We recently expanded. I touched on this already a little bit, but we expanded with 40 additional account managers. The sales team right now is 300 account managers. That expansion completed in the first quarter. Essentially, that allows for smaller territories. That allows us to, for the HCPs that we've been engaging with or calling on, detailing, allows us to see them more frequently and allows us to see additional targets. That would be in primary care.
That work continues to evolve as we get further out into further into primary care. That's underway.
Got it. You mentioned the long-term guidance of $1.5 billion - $3 billion, I think. Can you talk about sort of what goes into the lower end, what goes into the top end? How much of that is driven by expanding coverage from 63% up? How much of that is driven by greater expansion into the primary care? I mean, are there other factors that sort of fit into that, potential pricing dynamics?
Yeah, I think all of that. You can, I think, all of that when the confluence of those factors, which frankly, it's still the early days, right? We have runway to 2039, early 2039, which is fantastic. That's a very long time for you to see synergy across some of these developments that you mentioned, access, utilization management, expansions with respect to trial, and then potential uptake and prescribing behavior changes. We're very comfortable with that as a floor, right, and it becoming a potential blockbuster. We're very comfortable there. The range is such that when some of these things might occur, that just impacts the slope and ultimate trajectory. We'll continue to refine that potentially as things move forward. We have a better line of sight into what we think ultimate peak is.
We feel very good where we are right now.
On that 2039 runway, you guys had a settlement with Teva. I guess, how confident are you that that 2039 is the runway and that there can't be anyone coming in earlier?
Sure. Teva was the only first filer under Hatch-Waxman. There were no co-first filers. There was no process where we had to settle with multiple parties or a settlement with one. There was still ongoing litigation. Teva was the only one. We can talk about why that is. Because they are the only co-first filer, that sets the entry date. The patents go to 2043. The agreement with Teva is that they would be able to enter the market in 2039 with pediatric exclusivity or the end of 2038 without that.
Got it. Maybe shifting gears to Alzheimer's agitation. You guys have four studies, three of them positive. Maybe we can start with what's left for you guys to complete in the package before it gets submitted to the FDA?
It's the lift of building the package, which is primarily writing. The data generation, the patients aren't being treated. The clinical studies are done. That's great. It's compiling the data. It's incorporating the clinical study reports. It's completing the integrated summaries. It will be an sNDA, right? That's an efficacy supplement. We're only updating certain modules of the initial NDA. It's the build-out. We're tracking very nicely. We remain on track to a 3Q submission.
Got it. There's been a lot of discussion over what's necessary for the FDA to see for that package to be approvable. Can you remind us sort of how those regulatory discussions started that led to the next set of trials that you ran? If there's been any evolution since you've had those readouts? I guess, ultimately, how confident you are that having the three positive phase three trials is sufficient and that one trial that missed is something that just happens in the next thing?
Sure. The feedback, the history of that is the very first trial we ran was ADVANCE-1 . That was a parallel group trial. That study was positive. When that read out, we spoke to FDA and shared top line with them. That is what led to breakthrough therapy designation for the program. The feedback we've received, or we received and that we've received throughout the program, which has been consistent, is we need two adequate and well-controlled studies. We want two positive, adequate, and well-controlled studies. If it's helpful, I can walk through the exact evolution of how the trial started. What we have now with the package is three positive studies. We have another parallel group study, which is great and is consistent with the other three.
We have a standalone long-term safety database, which we needed because it is an elderly patient population. FDA asked us to generate a standalone ICH safety database with a certain number of exposures for 12 months, 6 months. They also, importantly, wanted randomized controlled safety data, which we have coming from two studies. That is ADVANCE-1 and ADVANCE-2. Feedback has been consistent and has been robust during the clinical program. This spring, we shared the pre-NDA meeting minutes and the outcome of that, which enabled us to file. We feel good about the package that we have. We are excited about the work. As I shared, we are on track to the 3Q target of submission.
Got it. I think a lot of the debate centers at times around having a randomized withdrawal study versus the parallel design randomized control studies. I guess, is there any difference in the way the FDA views those two study designs? Is there any difference in the way, ultimately, physicians look at the data coming out of those two study designs? Or is it sort of the same for regulators and physicians?
I mean, they are different designs. It may depend on, with respect to the FDA and being able to make an assessment of efficacy, no. There is precedent for that. There is written guidance for that. There is also the feedback we've received about the nature of the package. We feel good about that, precedent even within the division of psychiatry and across prior programs. It is all consistent there. When I initially started, that it depends is they are different types of studies, right? They can tell you, right? Parallel group, you can track longitudinal change, right? You do not do that with a randomized withdrawal design study. There, you are essentially looking for maintenance of effect, durability of effect, or removal of a treatment response. You can see different things. In terms of demonstration of efficacy, both can do that, right?
That's important. There are differences with respect to the type of safety data that come out of those. That's why I mentioned we needed the two randomized parallel group trials, controlled parallel group trials. That's ADVANCE-1 and ADVANCE-2 . Because FDA wanted, in addition to the ICH safety database, they wanted the controlled data. That helps. That does provide, those trials do provide a different type of safety assessment versus randomized withdrawal where everyone is treated in an open label fashion with the product before they're randomized.
Got it. What do you think the launch curve for Alzheimer's agitation might look like? What parts of the product are going to resonate most and help drive that uptake?
We haven't quantitated that. I mean, internally, there's modeling, of course, and that informs the targeting assessments that are underway right now and vice versa. We've shared that we think peak is similar to depression, say, $1.5 billion-$3 billion. So we've offered that. In terms of quantitating, I think that's we'll have to see how it goes in the early days. We feel very good about the current infrastructure and team that's in place. Many of the HCPs that the team is engaging with now are appropriate and there would be overlap in those with HCPs that we'd want to engage with if the product is approved for AD agitation. That work is well underway.
We feel good about impact that should the product be approved, that it's a relatively quick process to start engaging and detailing on the new indication.
Got it. Shifting gears to SYMBRAVO, which is a product you're going to be launching at the end of the quarter, actually. I guess, can you talk about how you're thinking about that launch strategy, who you're going to be targeting? Is it going to be more specialists? And maybe how we should think about the contribution from SYMBRAVO this year?
Sure. You're right. We'll be launching next month. The countdown clock is underway internally. What are the next steps, just practically? The sales team, it's going to be about 100 reps. They've joined, and they're going through training and onboarding right now. That's great. That's the rate limiting step. We will be focused on specialists. It's a discreet sales team for migraine because we'll be focused on headache centers. Throughout the U.S., that will be the initial call point, if you will. We'll go from there. Right now, it's going to be looking to facilitate trial and utilization with patients who are seen by headache specialists.
Got it. There have been a number of different launch strategies in the migraine space. You had sort of the high gross to net discounting early on. You guys took a very different approach with depression with AUVELITY. How should we think about that end of the strategy? Is it going to look more like what you've done historically in the past?
It will in terms of having a very, say, disciplined approach for identifying the areas we want to be in from a territory perspective and then who we want to be calling on within those territories. That differs from trying to go as broadly as possible into primary care as quickly as possible. Now, with that, the payers manage the utilization management for migraine. It is distinct for depression, right? Nearly every payer requires a PA to label. Confirmation of age and diagnosis. In a similar fashion, nearly every payer requires, say, at least one generic triptan step. It is different from depression. Sampling strategies are different.
Depending on the case studies you mentioned or, say, the launch strategy, there can be different strategies to patient savings and patient support wherein to help get appropriate patients the medicine, if they're prescribed it, to make that process easy. We'll have some of those things in place. I would say how long the duration of those for any given patient or the amount on an annual basis, those things will be, I think, will look a little bit different. They will be in place. It is distinct from depression. I think our approach will be kind of in our vein or our kind of the Axsome way of looking to have a data-driven deploy capital in a very disciplined fashion. You'll still see that, but within the migraine category.
Yeah. You guys have a lot of programs. It's a lot to cover in 25 minutes. I wanted to shift now to SUNOSI, solriamfetol . You guys had two different phase III trials read out in short order, maybe starting with ADHD, positive data there. Next steps are to run pediatric studies. I guess maybe two questions. First, what's the translatability usually been from an adult study to a pediatric study in this indication? I guess, how de-risking is the data you've shown?
Yeah. I don't have a coefficient for you. But generally, the two go hand in hand, right? Not always. But oftentimes, if you have activity in adults, historically, that indicates the molecule's active. And then running a pediatric study, it ties to signal detection and the type of study. But generally, they go hand in hand, right? Not always. Our job is to determine that, right? That's the next study. That's on track for 2025. With respect to a potential package, the feedback we've received from the FDA is we need two studies, one adult and one pediatric adolescent trial because the initial indication we'll be targeting is both adults and pediatric patients.
Got it. I guess, what's remaining to launch that pediatric study? I know at one point last year, you were talking about potentially starting that in parallel with the adult study. Now, it's sort of shifted into this year. Yeah. Can you talk about maybe what's left on the design and getting that running?
Yeah. It's really just the clinical development and clinical operations prep work for protocol, just get everything lined up, protocol, clinical trial material, things like that, some of which are lined up already. It's us just running air traffic control on the clinical side of the house and choreographing what studies are coming online. Of course, I don't think, of course, anything else. I think that we'll be providing an update there. The work is well underway.
Yeah. And then the other study you ran was in depression with EDS. Can you maybe talk a little about the strategy here? I mean, should we be thinking about this as EDS with comorbid depression, more depression with comorbid EDS? Are you going to be launching multiple parallel phase IIIs given what you saw or sort of one at a time, staging it more?
That's a good question. It will be major depressive disorder with excessive daytime sleepiness. Individuals who have major depressive disorder and also have excessive daytime sleepiness. We looked at MADRS. We'd expect to continue to look at that. We'll be starting the first study. Likely, we would need two studies, right, just consistent with the first was a proof of concept. We like what we saw. Obviously, that warranted additional work in the next phase III. To answer your question, we do think, as per usual, two studies would be needed.
Got it. In the last 10 seconds we have left, wanted to sort of zoom back out, bigger picture on the company. You guys launched seeing a top line number this year, $500 million-$600 million. Are you guys thinking about profitability, reaching breakeven, sort of the next step for the company?
Yeah. I think that's in sight. We haven't guided to a specific quarter. With the resources we have on hand, that was $301 million at the end of the first quarter, that enables us to reach cash flow positivity. Just in the company and the foundation and the impact to patients, the potential value we can deliver to shareholders, it's the best position we've ever been in for the company. Cash flow positivity is in sight. Our job is to keep putting on the elbow grease to continue to deliver on the commercial, regulatory, and clinical fronts. That's what we're working on this year and beyond.
Yeah. Sounds great.
Anytime.
Yeah. Thanks so much.
Thank you.