Welcome to the Cantor Global Healthcare Conference. I'm Pete Stavropoulos, a biotech analyst with Cantor. With us, we have Axsome, a company I cover. I am pleased to introduce Nick Pizzie and Mark Jacobson of Axsome. Let's start off with a brief intro of yourselves, snapshot of Axsome, and the company's focus and strategy.
Thanks for having us, Pete. Mark Jacobson.
Nick Pizzie, CFO.
Axsome, CNS-focused biopharma. We have three commercial products, which we'll of course focus on with the flagship at the moment, and all eyes are on AUVELITY, which is approved for major depressive disorder and recently Alzheimer's disease agitation, which we are launching. We've done expansion around that, and right now it's all commercial performance for that product and the two others, SYMBRAVO for migraine and SUNOSI for excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. Behind those products, we have a very deep and broad balanced pipeline of programs that are NDA stage. That's AXS-12 for narcolepsy. We have a PDUFA date of May 1st there, and multiple phase III programs, either with one positive phase III trial or that we've just initiated and are looking through various readouts. We can touch on those. It's an incredible time for the company.
The company's better positioned, and the fundamentals are better than they ever have been, and right now it's all about execution on the commercial and pipeline side of the house.
All right. In terms of catalysts that are coming up on late-stage assets, what should we expect in the remainder of 2026 and 2027?
Remainder of 2026 from a pipeline perspective, we've recently initiated a number of phase III trials. We'll get into those, but looking towards between now and the end of the year, we have the ENGAGE phase III trial of solriamfetol, that's SUNOSI, in binge eating disorder. We've guided to top-line results in the fourth quarter. We're looking forward to that. We like that program and the three other label expansion efforts or potential label expansion efforts that are ongoing now. Those are, real quick, major depressive disorder with symptoms of excessive daytime sleepiness, shift work disorder, and ADHD. That's the next pipeline event. Then looking to next year, I've touched on the NDA, the PDUFA date for AXS-12 and narcolepsy. Again, that's May 1st, and then we also have guided to top line from the shift work trial of solriamfetol in 2027.
All right, so you're also laying the foundation for the next wave. You have ongoing phase II/III's, as well as those that you plan to initiate. Just walk us through those.
Sure. I will touch on the recent initiations, which I alluded to. We have AXS-05 in smoking cessation. We just initiated the SUMMIT phase III trial. That is AXS-05 versus placebo and versus bupropion. Again, that we just started. We haven't guided to top line yet, and enrollment is underway, and stay tuned for updates there. Just prior to that initiation, we initiated two trials with solriamfetol and ADHD. We have a positive phase III trial in adults with solriamfetol and ADHD, and we saw a substantial improvement in adults in symptoms of ADHD, and now we need to complete studies in children and adolescents. Those are ongoing. We will provide updates there and top-line guidance once enrollment is really underway and we have a sense of how that's tracking.
The other trials that are underway, we have, again, I touched on the shift work disorder trial, and then there's the trial in major depressive disorder with solriamfetol. We haven't guided there yet either. That study enrollment has now been underway for a number of months. Looking at AXS-14, that is esreboxetine, so the SS- enantiomer of reboxetine in fibromyalgia. That trial we initiated a number of months ago now, and is enrolling there too. We will have updates for all of these programs. We're really excited about them, and if you look even earlier in the pipeline, there's AXS-17 and AXS-20, both of which are our programs that are relatively new to the pipeline, which we added last year and early this year, and tech transfer activities are underway.
Those are programs that were AXS-17 we're looking at for epilepsy and AXS-20 we plan to start a phase III trial in schizophrenia as the next program there, and we're also interested in exploring that for Tourette syndrome. Just a lot going on, different therapeutic categories, all highly complementary and have leveraged the clinical expertise that we've built over the years, and we will look forward to keeping you posted on them.
I'm surprised you can keep all of that in.
Yeah, no. It's- there, I'm sure I forgot something.
All right, turning to AUVELITY, you recently increased your peak sales potential in MDD in combo with Alzheimer's to greater than $8 billion. What are the assumptions behind that greater than $8 billion opportunity?
Sure. Yeah, I could talk a little bit about MDD to start with. We ended the quarter Q2, $180 million, so annualizing $720 million. That was with less than 0.25% of the total market share. We recently expanded the team from 300- 600. We also now have an LTC team that will be detailing or is detailing on MDD as well as ADA. We feel that if you take a look at the $8 billion and you split that up roughly 50/50, $4 billion, that's only 1%, a little bit north of 1% of the entire antidepressant market. What we've been able to achieve thus far with roughly a significantly smaller sales force than a lot of our peers.
That's why we decided, "Hey, let's double the team and let's take advantage of it." We have exclusivity through Q1 2039, if we get the pediatric indication for AUVELITY. There is a long runway, an additional 12 years that we have the ability to get to the $4 billion for MDD. When you take a look at ADA, obviously it's an untapped market with just one other branded agent in there that's an atypical antipsychotic, and we have just launched that. We're really pleased with some of the performance that we've seen thus far. There's north of 20 million scripts that are written each year in this indication, and we feel that the market is for our taking, and like I said, we just launched in the community setting, and we are launching in the long-term care setting.
All right, so with the recent approval and launch, like you said, it's a very large opportunity, meaning ADA. You're still early in launch, but what are you sort of seeing and learning from the first several months of launch?
The first thing we always look for with a launch is feedback from prescribers who have tried the product. We're starting to get back that feedback, it's starting to come in for prescribers, the early prescribers for AD agitation. Of course, we've been getting that feedback now for major depressive disorder for some time, and we're seeing a very consistent theme and category of feedback, which is that patients who are starting on the product are seeing important reductions in agitation. It's occurring quickly, and the tolerability profile is very, very good. Feedback we're getting from clinicians who are interested in the product or haven't yet, or who have, is that a key consideration and differentiator is the tolerability profile is very much of interest because it's an at-risk patient population.
The tolerability profile or the types and rates of AEs that we saw, very moderate in nature, and of course, the product does not have a black box warning for mortality risk in individuals with dementia. That's driving interest in terms of the feedback we're getting, and so that's great. The early trial so far is lining up with the data we saw in the clinical program and that's great. That's leading to additional interest in trial, and then that filters into the sales team strategy and tactics for who we're looking to engage with in terms of from education to provide samples to. All of that work, all those gears are turning, and we like what we're seeing so far, and we'll keep it going.
We expect to see impact from all that work start to grow and build materially between now and the end of the year and beyond.
All right. There is off-label use of generic antipsychotics in this indication. What do you see as the biggest barrier to shifting prescriber behavior to drive adoption of a branded therapeutic?
Well, I think part of it is just education, right? The utilization of off-label products or products off label for the indication is due to the historical lack of approved treatments. Now there are two approved treatments and both very different. That's great because there are different patient profiles and different needs. I think it's very basic and again, corresponds to our efforts, which is education and of mechanistic education, scales, and diagnosis and patient profiles. That's the team's job, that's the sales team members, that's their job, the medical affairs team members, that's their job, and of course, they're able to engage and educate in different ways and be available to prescribers to answer questions.
I think that's the bulk of it is just that it's not that those products that were used off label were necessarily incredibly effective, but rather the need, the clinical need is so large and the impact of agitation is so substantial, eventually it would get to the point that intervention would be required to prevent those individuals from risk and harm to themselves and others. Now that there are multiple approved products and AUVELITY in particular, we're very excited about its profile. We think that will lead to changes in prescribing patterns, and we're starting to see that now.
Awesome. You did highlight that 126% increase in NBRx among patients 65 and older. How should we interpret that from your perspective? How do you interpret that? I know-
Sure.
[inaudible]
Yeah, I think that's the first leading indicator is the NBRxs. Another metric we've been sharing recently is that prior to the approval, the NBRxs related to the 65+ Medicare LTC, they accounted for 19% of our NBRxs. The month prior to launch, basically that cohort accounted for roughly 19% of our NBRxs. Most recently now that's north of 30%. We're seeing that growth in NBRxs, which will ultimately transform to TRxs. The way that we think about the growth and the demand for ADA is it's the NBRxs that you're seeing in the titration packs that get reported, and everybody's looking forward every Friday to seeing what those numbers are. But it's also the samples that we're providing to the doctors. The amount of samples that we are providing to the doctors is significantly higher than what you're seeing out there reported through scripts.
Those samples ultimately, as I shared, will convert to a TRx in some fashion. We're starting to see the inflection in TRxs the last couple of weeks in Symphony and IQVIA data, and this is also at a time that's kind of more of a barren time in the psych space. That mid to end of August is usually a quieter period, but we're seeing that growth through this more difficult time period. As September, October comes around, we should be able to start seeing the conversion of those NBRxs to TRxs. The reason why we're doing sampling is we're heavily sampling, and we continue to sample in MDD as well, right? Doctors always want to try new patients on samples first, especially this cohort or patient population that's 65 and older, that's a little bit more fragile.
They want to be able to sample, try it, see how well it works, and then they will be able to either, A, write the script for another titration pack, perhaps, if they see fit. Or they can write a script for the maintenance dose. Either one of those will come out as an NBRx.
The bottom line is probably underestimating because of the sampling.
Again, we're defining demand as what we see demand and interest in the product is between what the patient is getting through a script or what the patient is getting through a sample, and that sample is just a temporary process that will eventually convert into a script.
Okay. How should we be thinking about adoption in a community setting versus LTC, both in the short term and in the long term?
The snapshot of the market now, agnostic to any product, is about 60% of the scripts come from the community setting and about 40% from long-term care facilities or a long-term care channel. For us specifically, what we would see in the short term or right now is that we'd expect the majority of the scripts to continue coming from the community setting, and that's just because that setting is further ahead from an infrastructure perspective. The time from a potential, say, detail or call or educational effort to a potential script or a sample, and then to a script, that's shorter than, say, the activation that happens in long-term care. As a reminder, our commercial team and infrastructure, there was no long-term care component previously. We were not engaging with long-term care facilities prior to the approval. That's underway now.
But that environment or that channel, it's much different from a community setting where there are prescribers and an account manager or a sales representative may go in, engage with a doctor, and then that doctor, if they end up being interested in trying the product and they have an appropriate patient that comes in or a relevant patient profile, then they can write it. That's kind of all there is to it. In long-term care, there are multiple stakeholders in the process before someone in a facility may have a prescription and then the product administered to them. So there's potentially a pharmacy network or a central pharmacy, and there are stakeholders and decision-making and a gating process there.
You have directors of nursing who are involved in overall prescribing decisions, and then, of course, clinicians or HCPs who either may be affiliated with a facility or a network of facilities or are, say, a community-based clinician who essentially does a rotation into these facilities. So the jargon is that these facilities are activated or brought online. That takes usually at least a month before there's the general ability for a prescriber or a clinician to prescribe or write in that setting. Simply in virtue of the fact that we weren't doing that previously, there is that lead time, but then once that occurs for any given facility, we'd start to expect to see writing there. Then that'll lead to kind of a differential mix between scripts coming from community and LTC versus what you see for the current kind of background rates.
But we'd expect that to grow and change over time.
All right. Anything else to touch on the Alzheimer's launch?
Just that we are really excited about it and we are really looking forward to keeping folks updated. As you alluded to, we know everyone is really interested in weekly Friday numbers, and we expect those to continue to, again, grow between now and the end of the year and beyond. It is great to have the product and the feedback that we are getting now and see its potential utilization grow over time.
All right. MDD growth continues to build. Main drivers of that, primary care uptake, increase the prescriber confidence. Anything you can tell us?
The MDD, I do not want to use the word status quo because that maybe suggests lack of activity, but MDD, we are still seeing very high demand and interest and uptake. You are right. From launch, the focus was to start engagements and focus activity in higher-prescribing psychiatrists. Then we have broadened out from there. What we see is once there is trial and a certain number of trial for any given prescriber, the feedback, similar to AD agitation, has been very robust that the product works well, it works rapidly, it is durable, and then it has a distinct safety and tolerability profile, which is leading to very positive feedback on the product and how it performs. That is driving uptake. Nick touched on where we expect to be from, say, at steady state from penetration. We are at about-
Yeah, right now with NBRxs, we are at 42 basis points, so 0.42% of 1%, which is a leading indicator of where we would expect the TRxs which is just under or just right around 25% of 1%, so 0.26%. That will give a good indicator. The NBRx market share of 0.42% gives us a good indicator, and that 0.42% is really just getting under the way with the expansion, right? We are expecting that number to grow and grow pretty significantly.
One of the reasons why we wanted to do the expansion was to have better depth with the high decile doctors. With 300 reps, it was hard to be able to get in front of those high decile doctors as frequently as they need to be. The more that you are able to detail and share the benefits of AUVELITY, the more likely that doctor will think about what patient is the right fit for AUVELITY. It is also just depth.
We are actually reaching more docs, more primary care, where we really think that that is how we are going to be able to grow the business.
Do you want to touch on access quickly, too?
Sure, yeah. Access, the great thing about access is it has improved, and it has evolved over the last even 12 months. Right now, there is 89% total lives covered for AUVELITY, of which 100% specifically in the government channel, which is obviously important for ADA, 82% in the commercial channel, and we are at north of 55%- 56% that is for first-line or first switch. Access covered lives is at a really nice level right now with great formulary access. Just going back to ADA, if we think about that 100% total covered lives, the majority of them, north of 85%, have no PA and are either also first line or first switch. If a doctor does find a patient, it is very likely that patient would be covered and would be able to get the product.
Going back to your question about just growth in MDD and continued growth in MDD, there's the sales force expansion. Nick touched on how that allows us to increase depth and breadth with potential prescribers, but then access is at a point that as we go further into primary care, that tends to be earlier line utilization, so first, second line utilization. The access is now at a point where if it's written in that setting, it can generally be filled. That lines up nicely and same point Nick just made for AD agitation. If it's written, generally, there are very few barriers to it being written and then filled.
Yeah. The setup is perfect for the back half of the year, right? We did the expansion. The team's now got on average four to six months, probably about four to five months of tenure now at Axsome. The market access is there. We're doing direct-to- consumer advertising. We might tick that up a little bit towards the end of the year just to kind of get the pull-through. So the setup is there between the ADA and the MDD expansion launch.
All right. I'm sure we could spend another hour talking about AUVELITY.
Sure.
Let's just turn to AXS-12 and narcolepsy. So moving into you have a PDUFA date on May 1st. You've highlighted AXS-12's rapid onset cataplexy reduction, cognitive benefit. How do you sort of see this fitting into the current NT1 treatment landscape where polypharmacy is common but also on the backdrop of the orexin 2 receptor agonists entering the treatment landscape?
Sure. So of course, let's get the product approved first, and that potential milestone is coming up, so that's in the first half of next year. Without the benefit of an approval and a final label to let you know exactly how we expect it to fit, you alluded to the product profile, right? We've focused on cataplexy as the primary endpoint in our clinical program. We also looked at excessive daytime sleepiness, which we saw benefit and improvement in, and cognition, also saw a cognitive benefit. Then you touched on rapid onset of action. We have daytime dosing. We have, likely a very different scheduling from the primary product or products that have been utilized for this indication. Then the tolerability profile is distinct from what's available, and products that have recent approvals or other products that could be approved.
So kind of depending on, again, your point of reference, the product's differentiated, which is great in what we're looking to do, and we think that all stems from the mechanism is differentiated. Mechanistically, it's differentiated from what's available in other programs in development, and that's important. It is an orphan indication, but as far as orphan goes, it's not ultra-orphan, and there's a pretty dramatic need for new treatment options. Of course, there's a lot of work now by the industry, which is fantastic. So we're excited about the profile again as something that's differentiated, that can be a potential, we'll see if it's approved, but a potential treatment option to fit in kind of that you alluded to. You mentioned NT1, so that'd be the area of focus.
No, I would just maybe add, it's super synergistic.
Yeah.
We have obviously, the sleep expertise now in-house with SUNOSI, and we've been detailing that, marketing that since 2022. So the team can essentially, if we wanted to add that directly to the bag, so minimal additional operating expenses would be acquired, and everything would just incrementally fall to the bottom line. So from a financial perspective, it makes a lot of sense.
All right. AXS-20. In April, you announced that you acquired this PDE10A, phosphodiesterase 10A inhibitor from Takeda. What exactly attracted you to it?
Sure. Well, there are a number of things. We tend to, I think it probably comes across in how we always go back to mechanistic differentiation. To us, that's really important, and how do you offer innovation to patients and prescribers? To us, that always starts with the mechanism. Here we have a potential novel mechanism for schizophrenia. We also mentioned that we're interested in exploring potential applicability in Tourette syndrome. You have mechanistic rationale, and you have clinical rationale. There's a phase II trial in this indication that was completed that we see a signal that warrants additional investment and experimentation. The plan here is to conduct a phase III trial in schizophrenia as the next clinical work for that molecule. You mentioned we acquired that earlier this year.
Right now it's about tech transfer and phase III-enabling work, and that work is underway. We're really excited about it in terms of just the overall need for that space. There are some products approved, of course, but there is still a need for novel programs. We'll continue the clinical program to see if there is a signal, and it may be efficacious, and what the tolerability profile may be. That is highly complementary to the products that we have in our commercial portfolio and those that are in development. It also is complementary in terms of if we ran through the pipeline, which I appreciate, because oftentimes we don't have time to do that. It really helps us balance the pipeline, which historically was very late stage and lopsided towards phase III.
Now we actually have things that stack in that are earlier stage. Of course, this is phase III-enabling work, so it is not that early, but it fits nicely with the other programs that we have in the pipeline.
In terms of tolerability, any AE profiles? From the phase II, one of the problems with drugs in schizophrenia, right, is tolerability. Then they cycle off. Is there anything that suggests that?
Well, yeah. If you look at the rates of AEs and maybe classic AEs that are considered, that you often see in terms of movement disorders as one example, there may be differentiation there. We have a limited data set so far. It is not that limited. There are quite a few patients in the phase-
160?
Yeah. I do not mean to diminish it too much, but there is still more work to do to see how much differentiation there may be there. But you are right. That is another compelling component, and again, we would tie that to, most likely due to the different mechanism that the product has.
All right. We are out of time. I want to thank you both for participating in the Cantor Healthcare Conference, and looking forward for more progress and-
Yeah. We will definitely do that, and thanks for having us, Pete.
Appreciate it.
Really appreciate it.
Thank you.
Cool.