Hey, guys, I'm Matt Hershenhorn, one of the biotech analysts here with Oppenheimer. Welcome to our annual healthcare conference. With us today, I have the pleasure of hosting Nick Pizzie and Mark Jacobson from Axsome Therapeutics. We're gonna do a fireside chat today. If there are any other questions, please do email me, and I can try to work that in. Without further ado, we could get started. Mark and Nick, thank you so much again for joining us today. Great timing with your 4Q update on Monday. We thought we'd start just by discussing the core business for Auvelity in MDD.
Congrats on achieving over $500 million sales in 2025, only three years since the launch, I guess considering the current momentum, could you just talk about what's driving that and where you see it going in 2026? We know a big update was the recent sales force expansion. If you could just talk about how that could drive, you know, further uptake and with 600 reps total now, what the ROI on that could look like? Just curious and really appreciate it. Thank you.
Sure. No, and thanks, Matt, for having us. We're happy to be here and you're right, great timing, coming off on Monday. You know, when you look at Auvelity, just to jump right in, the past year, we just saw continued uptake and demand across kind of all the segments and targets and patient types that Auvelity is being put in front of.
In particular, we're seeing trialists become adopters, we're seeing adopters become advocates, and all of that is fueled by or driven by the improvements in market access that we saw over the year and by a very small sales force expansion at the start of last year.
As a reminder, about a year ago, we expanded the sales team by 40 reps to approximately 300. That alone, along with, you know, market access and again, just trial, led to the results that we saw over the year. That's really what's driving the continued investment by us for the expansion that you mentioned. We'll be expanding to 600. The reason for that is the opportunity still remains substantial, especially as we go into primary care.
We saw the largest growing prescriber segment in primary care, and we're barely scratching the surface of the market, and so it's with that in mind and the potential for the product to continue to impact patients and to get in front of other clinicians and nurse practitioners, that's behind the decision to expand again.
That, by the way, is also. It achieves multiple objectives, right? Then obviously, we're on the cusp of FDA's PDUFA date for our sNDA for Auvelity in Alzheimer's disease agitation. This is anticipatory for, you know, it's pre-launch activities there as well. It does both, it scratches both itches, so to speak, and is a great way to, you know, start off the year.
Got it. That makes perfect sense. Yeah, we'll definitely get more into the ADA opportunity. I guess, for now, just thinking about the trajectory for Auvelity within MDD, and considering the current depression treatment landscape and where Auvelity slides in, considering its differentiated benefit-risk profile, and especially as you mentioned, further uptake within PCPs.
I guess just curious, you know, what's driving, you know, uptake there, generally speaking, but then also especially within the first line or first switch subset of patients? If you don't mind also, to talk about kinda just where access and reimbursement is now with, I think high 40s GTN for 4Q, and kinda how you generally think of balancing access and volume, along with improving that revenue per script since the launch into 2026.
Yeah. Sure, Matt. Maybe I'll take a little bit on the numbers first. We're around 86% commercially, 86% total covered lives, 78% commercial, 100% in the government channel. I'll share a little bit more on the government channel, why that's even more important with ADA, in a minute. As it relates to GTN for Q4, as we shared, was in the high 40s% for Auvelity.
We look to 2025 as a good proxy for what 2026 would look like from a GTN perspective. As a reminder, in Q1 2026, we were in the mid-50s% range, you know, we would expect that to be in that similar range due to seasonality. Market access has obviously evolved significantly.
It's improved in the amount of lives as well as evolved in the quality of coverage, from the time that we started with MDD, 13 quarters ago now to where we are with 86% covered lives. We're pleased with that, and importantly, 50% of our total scripts are in first line or first switch. When we talk about quality of coverage, it's important to talk about GTN, but it's also important to talk about the quality of coverage.
The other, the first part of your question about what's driving uptake, you know, there are a few elements of that. One is just our expansion into primary care, we're engaging and the product is being detailed for new targets or existing targets more frequently. One is just awareness and trial, the other element is remains the product profile, which is that highly differentiated and that patients are having great outcomes, and that leads to continued, right?
That's the dynamic I mentioned earlier, where trialists are becoming adopters, and then that cycle perpetuates to adopters becoming advocates. It's the product profile and then execution.
Sorry, got it. That makes perfect sense. I know one element of the story is just in terms of how long patients can stay on therapy, and for sure, a function of physician experience, and I'm sure also the side effect profile. Do
you mind to just talk about, you know, kind of what that average retention rate currently might look like? Also just how you view, you know, the ability for patients to continue on therapy, or if they come off, is that because they're doing that much better? Just curious, I guess, kind of how you view that and if that, you know, confers a distinct advantage.
Yeah. So persistence, we haven't shared a discrete number yet, and the reason for that is we're still monitoring that and that is due to the different patient profiles the product is being used in or trialed in. You know, obviously, that's been evolving pretty dramatically since launch, where in the very early days, it was a later-line patient. Now over 50% is first line or first switch. You know, it's around 15% or north of 15% first line. Then the you know, 35% or just under there, first switch, which is great.
All that being said is right now we're tracking in line with what you typically see for antidepressants, and there are probably a number of reasons for that. Again, ties to the line of therapy, how long patients are on, if they're entering remission quickly, or.
The decision is, do you stay on product to stay in remission, or do you come off to reduce, you know, being on medication? Those dynamics are playing out right now. Team's watching them, and I think as something more discrete or where we have more precision around that number, we'll share something.
Okay.
We're happy with what we're seeing now. Of course, that's also part of what leads to the performance that we were referencing earlier. It's part of, you know, people are staying on product, they're doing well, you know, we're seeing growth from NBRx and also TRx.
Got it. That's really helpful. Thank you, Mark. We were also, just gonna talk about the ADA opportunity for sure. Congrats again on receiving the priority review from FDA. I guess just to start, if you don't mind, to share a little bit of background, just for those maybe less aware of what agitation within Alzheimer's disease actually looks like, how it's defined diagnostically, and why does that remain such a large area of unmet need, with only Rexulti approved so far? For sure, we'll get into what advantages Auvelity could bring to the table.
Sure. Agitation, of course, clinically and from a regulatory perspective, the CMAI, so the Cohen-Mansfield Agitation Inventory is used as a scale or instrument to assess agitation. That can be done, you know, clinically with prescribers, but it essentially boils down to, there are a number of subscales, and those tie to aggression, and that's physical or verbal.
You have non-verbal behaviors in addition, and those can be described as restlessness. You know, there are different types of that, and the CMAI is used to make that assessment, and that's what we used in our studies.
Then how clinicians do it, some adhere to the CMAI, but that's really more, you know, a clinical trial and regulatory element. It was initially developed for assessing patients in long-term care settings. That is, you know, why is the, you know, market where it is with only one approved product? That's because there's been very little innovation, and part of it tied to how do you actually measure agitation, so there's now a regulatory-accepted endpoint.
One product that's relatively new to market in terms of having a label for the indication, but historically, patients have been managed by generic off-label products, oftentimes atypical antipsychotics or antidepressants.
There's a lot of development and building out the market, now that there can be active promotion in the marketplace. We're seeing that, and the product that is approved for that's growing steadily, which is great that there are now on-label options for patients. You know, we're excited about the potential of Auvelity for patients in this indication.
Yeah, maybe a little bit on the size of the market. There's about seven million Alzheimer's patients out there. 70% or so experience certain forms of Alzheimer's disease agitation, so it's roughly five million patients there, and roughly 20 million scripts are written on an annual basis. Obviously, the bulk of them are written off-label.
Okay, got it. That all makes a lot of sense. I guess just thinking about the PDUFA date you have on April 30th, and the clinical data that you were able to generate, if you don't mind just reminding us, you know, if you could talk about that data set, what went into that filing, the sNDA, and how the overall data support your confidence in, you know, potential approval and broad uptake. If you could give a sense of, you know, the efficacy and particularly the safety data informing benefit, risk, and any advantages based on the clinical data versus Rexulti, that could play out in the real world, that would definitely be helpful.
Sure. We had a full clinical development program, and what I mean by that is the product is already approved, the FDA has weighed in on the safety and tolerability of the product. However, because this is an elderly patient population, the FDA asked that we generate a new, entirely independent, standalone ICH safety database.
The clinical package includes that. We had four controlled trials, three of which were positive. That's the ADVANCE-1 and the ACCORD-1 and ACCORD-2 trials. There was also the ADVANCE-2 trial, which is important from the totality of data, both efficacy and safety, and then the long-term safety trial, and the to generate the ICH exposures that were needed.
That's all in the package. When you think about the product profile and what we saw clinically, we had, from an efficacy perspective, two different trial paradigms. We had longitudinal parallel group controlled trials. Then we had two randomized withdrawal design studies. We can see in either trial paradigm, we saw a separation, and they tell you different things, durability of treatment and longitudinal change, right?
When you think about the profile in this patient population, we saw statistically significant separation at week three in the ADVANCE-1 trial. Then we also saw very durable responses in the ACCORD trials, as well as the open-label long-term safety.
From a safety perspective, like, again, elderly patient population, so there are certain signals that you want to be mindful of or look for, and we did not see an association or signal for falls or mortality. Overall, a very, a very nice safety and tolerability profile with the associated efficacy. We're pretty excited about it, and of course, mechanistically, you know, mechanistically, from a molecule perspective, very different from what's used on-label or off-label currently in this patient population.
Got it. Okay, that makes a lot of sense. I know that April 30th is coming up, almost two months away. If you don't mind just talking about how you're thinking through your go-to-market strategy, launch preparation, and once it's approved, just kind of what the cadence of the launch could potentially look like.
Any feedback you could share from physicians and payers, we understand it's predominantly a Medicare Part D channel opportunity. If you don't mind to just talk about, you know, what expected reimbursement could look like and, again, the trajectory, that would definitely be helpful.
Maybe I can talk a little bit about what we're doing pre-launch right now. First, we have a non-branded campaign out there, a website, to raise awareness around Alzheimer's disease agitation. Medical affairs team is working hard, MSLs, trying to educate doctors on the disease. From a market access standpoint, I think it's important to note, I shared this earlier, previewed it earlier, is, you know, we're in a spot going into Alzheimer's disease agitation.
That's a benefit that we had that we did not have with the MDD launch, right? Roughly 70% + of total scripts for Alzheimer's disease agitation will be in the Medicare Part D channel. As a reminder, we have 100% coverage in that channel.
One of the main hurdles that we had out of the gate with the launch for MDD was having covered covered lives, and obviously, had a patient service program to help support patients to be able to get product. Here, coming out of the gate from a launch perspective, we'll be able to have full coverage for those Part D lives.
Just maybe a note, probably, one of the next questions will be is on GTN and how we think about GTN and ADA. We expect each script in ADA to be have a better GTN than each script in MDD. Since the majority of the scripts will be in Medicare Part D, and there's no co-pay coverage, GTN will likely be more favorable in that channel versus the commercial channel.
You know, what we will see over time as ADA scripts increase and are weighted more equally to MDD, we should see an improvement in total GTN for Auvelity.
Okay, got it. That's really helpful. I appreciate that, Nick. I guess just the last question for now to round out ADA, just thinking longer term, we know there's other drugs in development, for example, Cobenfy, I think is undergoing an ADA trial, although we'll get the ADP data from them first, presumably now, this year.
I'm just curious, I guess, one, you know, why it still remains such an underserved area in terms of even clinical development. Are there other candidates out there, you know, the muscarinics and just kind of thinking through the differentiated modalities here? You know, one, is there potential for Auvelity in ADP? Secondarily, do you see any competition, or rather, how you see the landscape shaping out over time?
It's, so the, just why, you know, why the amount of innovation in the space, that's a little hard to comment on. I mean, we're certainly doing our part to deliver a new treatment option to patients, and I think you're seeing more of that, and it probably gets easier as paths, initial paths or pathways are tread. That clarifies things. There's regulatory precedent, there's input there, maybe it leads to additional development and-
Which, which would be a great thing? You know, you mentioned kind of this overlap with ADP. You know, clinically, those are, of course, very distinct, right? That's, that's hallucinations, delusions, and you do have some overlap in certain patients have symptoms of both.
We've always been very interested in Alzheimer's disease agitation as the keystone symptom that leads to placement in long-term care facilities, and that where family members or caregivers stop being able to take care of folks themselves. That's been a deep area of interest for us in addressing that area of unmet need.
You know, we haven't shared plans to target ADP as another indication for AXS-05, and right now we're very focused on the sNDA and getting this over the finish line and, you know, the PDUFA date coming up, which is we're pretty excited about. Then, you know, then we'd be happy to talk more about additional plans. I'm not trying to be coy, in particular, about ADP.
Mm-hmm.
You know, our focus in dementia is agitation. I think I would be remiss not to talk about or just since you asked about the potential of the product and mechanism for other areas of unmet need.
Yeah, and maybe just to round out.
Yeah
Auvelity, I mean, we've shared peak sales is in the neighborhood of $2.5 billion-$6 billion in totality. We believe that's very achievable numbers. These are not aspirational numbers at all. I wanna, you know, state that clearly. These we feel are very achievable numbers, and those numbers have not been updated. We get some questions on when we will update peak sales numbers. That's something that we're looking at. Currently, those numbers were shared prior to even launch, I believe, with a different fact set, and as the facts have improved over time, we feel very good about where we are as a company.
Got it. Appreciate that. Yeah, very comprehensive. I know that it's only Auvelity, and you guys have two other approved products in the whole pipeline, and I know we only have, you know, maybe, 7-10 minutes or so. Just considering, you know, potential near-term catalysts, we know we have the solriamfetol Sunosi expansion programs. I think BED, binge eating disorder, and shift work disorder trials are reading out this year. If you don't mind to just kind of remind us, One, you know, what the setups are for each of those in terms of the trial design and what you're hoping to see from the data there. Just curious, I guess, for BED, you know, what would quantify success?
Do you expect, in the base case, that you would need to run another phase III trial prior to filing for approval?
Sure. Binge eating disorder, just to maybe take it in reverse order, we're conducting a, you know, the first phase III in that indication right now. We expect top line in the second half of this year, you know, our current expectation or when we last aligned with FDA before launching this study, is that we would need two trials. You know, we'll see with the first one here, you know, we're excited to look at that. It's a 12-week study, you know, against placebo, we'll keep everyone posted on progress.
The other ongoing trial that's been ongoing for some time is solriamfetol in shift work disorder, that's a program wherein t op line is expected next year, by the way. That's a program where we've aligned with FDA that should that study be positive, we only need one trial to support potential label expansion. The reason for that is it's considered a related indication to the current body of evidence that's on the label, so those data are potentially supportive of an indication in shift work, hence the need for just one trial. That's moving along, and then actually just yesterday, we announced the enrollment of the first patient in the study in Major Depressive Disorder. This is a precision approach to MDD, wherein we're only looking at patients with symptoms of excessive daytime sleepiness.
We haven't guided to that yet because we very literally just enrolled the first patient. The first patient was just dosed, so screening has been underway. We'll see how early enrollment goes, then we'll be able to offer some guidance there. Our expectation is to have two studies for that package as well.
Okay, got it. Yeah, I'm glad you mentioned that. We did notice that yesterday, and congrats on getting the first patient dosed. I think it would be great now to just talk a little bit about AXS-12, just considering the filing coming up and potential launch, you know, potentially early next year.
Yeah.
Just curious, I guess, how you plan to leverage your current experience in sales force with Sunosi and EDS, for AXS-12 and your overall strategy within narcolepsy differentiation, competition, et cetera.
Sure. No, thanks. AXS-12, that's right. That NDA is going in imminently. We're about to press the button, and the synergy with the current sales force, we have a sleep sales force for Sunosi, and it's complete synergy there, and meaning that product, if it's approved, if AXS-12 is approved, that can go right into the bag of that team, and very little additional work that needs to be done. I mean, obviously, you'd have marketing material development and key message development, core visual aid, so on and so forth. The most important thing is the team, and the call points are already established and active, so to speak.
That we're very excited about, one, because it's at a differentiated profile from what's available and other programs in development, which is great, also the infrastructure is already in place, and we already have that experience for, you know, quote-unquote, "an orphan product". We're really excited about that.
It's by definition the plug and play. I mean, it's a creative very quickly upon an approval, you know?
Got it. Okay, that makes sense. Appreciate that. I did want to touch on AXS-17, just since that's a newly in-license asset for epilepsy, representing, you know, a bit of an expansion, but still squarely within CNS. I guess just curious, you know, kind of what motivated that deal specifically, you know, how it complements your current strategy. If you could talk a little bit about, you know, the potential competitive advantages there within, you know, if it's FOS specifically, or, you know, just broader adult epilepsies. Curious, I guess, also, more broadly, how you think of business development in licensing or even buying assets in general.
Sure. The reason for that, obviously, we've got an incredibly robust late-stage pipeline. You know, it's four late-stage product candidates, eight late-stage indications. There's a ton going on, and the team obviously is quite busy. The pipeline, when you think about the pipeline, is a little bit lopsided towards the later-stage programs. You know, you don't get a pick when opportunities come along or, you know, come on your doorstep, and this is one of those cases where, we became aware of this program, thought it was incredibly interesting. It. We were able to acquire it at a, you know, very, compelling, economic terms, and so, you know, Nick Pizzie can touch on that.
It really complements the development, the R&D infrastructure that we have in place and the commercial infrastructure that we have in place. We haven't yet confirmed the indication, the specific indication yet, so we know there's a lot of interest and speculation there. Stay tuned, we're going to do that as quickly as possible, and we're going through some of our assessments now to make that determination. 2026 for AXS-17, it's all about phase II enabling work, so that's coming, and we're excited about that. One of the prompts for us to move forward with this is the team here and a number of folks on the team, clin dev, clinical operations, they have deep expertise in epilepsy, so it also made sense from that perspective, too.
You know, there's the economic element, there's the CNS development element, and then there's actually the commercial element, too. That all made sense, and then plus, we have folks who already know what they're doing. It all there was a nice confluence of different factors that went into doing that.
Got-
You know, Go ahead.
Well, it's at 2:30, so.
Oh, yeah, okay. Yeah.
Please, I know we're kind of running up on time. Matt, feel free to continue.
Yeah.
Oh, yeah. No, sure.
Well, I have more to say on AXS-17.
Yeah, no, I mean, I'm sure we could talk for a long time about any one of your assets, but I did want to just use the last question, and thank you both so much again for your time today.
Sure
Just to cover anything else we might have missed. I know there is a lot in terms of Symbravo and migraine and the fibromyalgia opportunity and maybe just other, you know, high-level comments on the way you're managing the business, sightline to cash flow positivity. Just curious, I guess, anything else that you think the street might be missing?
Yeah, we need 1 hour, I guess, but maybe just to kind of summarize it on the financial side, you know, we talked about the expansion of the field force, which we're just essentially accelerating it. We've seen the success that we've had to date. We see what's, you know, in the near term ahead of us with the ADA filing acceptance and hopefully the approval, so getting ahead of that.
All that being said, still being able to have operating leverage in the P&L, which I think is important from a cash flow perspective, it doesn't change our guidance at all. You know, we still have sight, near-term sight for cash flow positivity.
I mean, even the last couple of quarters, we've been very close to cash flow positive, single digits, on a cash basis from a net loss perspective, and then on the near-term horizon, EPS positive. Nothing has really changed at all from our financial strategy, just really trying to accelerate now, accelerate scripts from a novelty perspective, as well as being prepared for the ADA launch.
Got it. That all makes perfect sense. Yeah, thank you both so much again. Definitely interesting times for Axsome. Thanks for sharing your perspective.
Yeah.
We really appreciate it. To our audience, thank you so much again for joining.
Thanks for having us, Matt.
Thank you, Matt.
Bye.
Thanks, guys.