With the next session, I'm Andrew Tsai, Senior Biotech Analyst at Jefferies. Thanks for tuning in. It's my pleasure to have Mark Jacobson, Chief Operating Officer, next to me from Axsome . Welcome.
Hey, thanks. Thanks for having us, Andrew.
Yeah, you got it. Maybe briefly introduction about Axsome, what you're working on, what your strategy is, and then maybe talk about some of these near-term catalysts you're looking forward to. You've got a lot of programs.
Yeah, sure. No, great. Thanks again, Andrew, for having us. It's nice to be here. Axsome, obviously, we are a CNS-focused biopharma. We have had a pretty eventful year. Just to set the stage, we now have three commercial programs, two of which we developed internally. One of those, which is about to launch imminently, is SYMBRAVO for migraine that was approved earlier this year. The other two products are AUVELITY for major depressive disorder and SUNOSI for excessive daytime sleepiness and OSA, so obstructive sleep apnea and narcolepsy. Growth phase for all of those, and we can get into specifics, but we're pleased with the commercial execution to date. Behind those, we have three NDA-stage programs. That's AXS-05 in Alzheimer's disease agitation. There is AXS-14 in fibromyalgia and AXS-12 in narcolepsy.
We can talk about each of those and the status of those programs. Then behind that, a number of clinical stage programs across a variety of CNS indications. Happy to be here and just field questions as would help. Balance of the year, I think the biggest activities are just continued commercial execution across the programs and attending to the NDA-stage work. Obviously, continuing to drive enrollment in ongoing studies and starting a few studies.
Great. As I think about your programs that could be approved over the next 12 months or so, I mean, there's a good chance for all of them. Let's just say they were all approved, launched as go as planned. I mean, you're a company that seems to focus on ROI as well and profitability. When do you think you can hit profitability?
No, thanks. We have guided to that with the current resources on hand and the current trajectory for the products on market that we expect to reach capital positivity. We have not yet guided to a specific year or quarter. Achieving that milestone is in sight, and it is not even on the horizon at this point in time. We feel very good about the operating plan and how we are deploying capital in a disciplined fashion. One key component of that is, you are right, we have three potential launches on the horizon in addition to SYMBRAVO, which we expect to launch this month. There is high synergy and internal leverage with the sales teams that we have in place and the commercial infrastructure that we have built. We would expect a number of those potential launches to be very efficient in terms of capital deployment.
Speaking of sales reps, can you give us some color around how many sales reps you have now for the existing business with SUNOSI and AUVELITY for major depression and how you expect the evolution of the number of sales reps to unfold over the next year?
Definitely. SUNOSI, it's about 75 reps, 74, 75 reps. That's been steady since we acquired the product a few years ago. I think for the time being, we anticipate that number to stay steady. Looking to the future, that's a sleep field for us. There's high applicability to AXS-12, the product candidate for narcolepsy, should that be approved and just adding another potential product to that team's bag. AUVELITY is currently at 300 reps. We recently expanded that from approximately 260 reps earlier this year in Q1. They're in the field now. They've been in the field since the end of the first quarter. We're starting to see that impact in terms of a step in new-to-brand script, so NBRx. We'd expect to see that pull through to TRx between now and the end of the year and beyond.
With internal leverage and applicability to future programs, of course, there's AD agitation and other indication or products that may be relevant. For the time being, we think 300 is right size. We're a data-driven organization. If it makes sense, say, upon potential approvals or fertile grounds for additional investment, we won't rule that out. Right now, we think 300 is the right number for AUVELITY and the psychiatry field for us. If you look at SYMBRAVO, we've shared that we'll be launching with an account management team, so the reps of 100 reps. They're on board. They're finishing training right now. Essentially, once they're done with training, they'll be in the field, and we'll have an update with respect to commercial availability.
Thank you. Maybe a couple of questions on AUVELITY, the ongoing launch performed very well. The question is, why are you confident this could be a multi-billion dollar opportunity in MDD alone, major depression alone? When I think about precedents like REXULTI, VRAYLAR, CAPLYTA, maybe they're expected to do in the $1 billion-$2 billion range. What makes you confident you have a multi-billion dollar?
Oh, sure. Yeah, no, thanks. It's where the data are pointing to right now and where we are. We're just north of two years into launch. Already, the run rate annualized is $400 million as of the end of the first quarter. It's based on just extrapolation of where things are today. Where are we seeing utilization? Already, we're seeing frontline use at about 15% of the scripts, second-line use at about 35% of the scripts, and then beyond. That's a great place to be. It's a great place to be with we're at 63% of covered lives in the commercial channel, about 78% total, so essentially 100% in the government channel. That's a great place to be with our expected continued evolution of coverage.
That is both additional lives covered in the commercial channel and then improvements in the current type of coverage towards reductions in utilization management. You would expect that to continue. Of course, with respect to the other products that you mentioned, AUVELITY is approved for MDD, so not adjunctive use. When you think about that, again, already from launch, we are seeing monotherapy use in more than half of patients already. That is a great place to be. It is really the confluence of those things and just the rate of scripts and NBRx that puts us to those estimates.
Right. You mentioned extrapolation earlier, which you did settle with the first and only filer a month ago, or not a month ago, but earlier this year for 2038. You have a long tail. Okay, that works.
Exactly.
As I think about 2025, the drivers behind sales, you've got new sales reps going on. You are, I believe, launching a national DTC campaign second half. What other drivers do you see?
Sure. The expansion, that's important because one thing we're doing with that, you're increasing reach and frequency of HCPs that you're engaging with. The increased reach here with what we're starting on now or increasing our efforts around is going into primary care. Scripts, it's about 20%, 25% of scripts are coming from primary care right now. There's a lot of work to be done there. That's a potential growth driver. You mentioned DTC. We do have a national DTC campaign that's in the works and could be rolled out as early as second half of this year. What we're doing right now, just to share, is that there are some regional markets that that ad is being tested in right now. We'll take learnings from that to inform potential national rollout.
We can do that in our, again, just disciplined, high ROI approach for something like a national DTC effort. Of course, that is one of the classic levers for potential growth driver. The other, we touched on this already, but it is a key consideration, is just evolution in coverage and that for potential appropriate patients, that if an HCP wants to write the script, it can be filled relatively easily. That opens potential volume drivers as well. Those are the three, I think, primary categories. That is elbow grease associated with each of those. That is a key focus of the team.
Maybe one last question about this launch. Grossing that, I think, was 55% for first quarter. Fair to assume it will continue to improve quarter over quarter for the rest of this year?
You do have that backdrop where gross to nets in general trend down over the course of the year from a seasonality perspective. Yeah, we said mid-50% and that we expect actually that to be relatively steady from Q1, Q2, and beyond for the year. Part of the reason for that is just that even though you have that backdrop where gross to net can improve over the year because of the nature of coverage evolving. When you have changes in coverage, they are chunky, right? That depends on how many plans maybe are implementing changes in the types of coverage and rebates that may be being accessed that we think would keep gross to net relatively steady for the time being.
I see. Stable. Okay. As this launch is going on, you're filing for the same compound and NDA in Q3. It could be approved if you have priority review maybe mid-2026. This is for Alzheimer's agitation. When I think about the other Alzheimer's agitation drug, approved REXULTI, the question would be, why do you think the sales of that compound have been slow? Maybe you think it's okay, but why would it be different for AUVELITY?
Sure. I mean, the team watches that. It's a little bit hard to speak to it specifically because obviously, that's not our program. If you look in the channel for AD agitation, in the government channel, Medicare Part D, those scripts are growing steadily. Maybe if you are referring to total scripts, I believe the product is growing, but the key growth maybe is where they're shifting their attention to in Medicare Part D. To us, it's informative. You're right that I think there are a number of key distinctions. One is just mechanistically the product is much different, right? It's an oral NMDA receptor antagonist. It's not an atypical antipsychotic. We think that's a key element. Should the product be approved, we would anticipate the label to have other distinguishing characteristics or considerations. Take Advance-1 , for example.
We saw separation in two weeks, which was stat-sig in three weeks. We have maintenance of effect studies. That is from an efficacy perspective. The safety and tolerability considerations or observations, the profile is distinct. We think that we really like that. We like the package we have. It is too early to comment on what a label could look like. Based on the data we have in hand, it is a different molecule and profile. We like that.
Yep. And REXULTI as an antipsychotic has a class black box warning for increased mortality. You don't think you'll get one. Is that correct?
That warning is for atypical antipsychotics. Obviously, the product is not one. We would not anticipate an atypical antipsychotic warning. That is the only product approved in the indication. Exactly, again, it's difficult to say, hey, the totality of labels look like this or that at this point in time. Yeah, with respect to the atypical warnings or contraindications, we would anticipate some distinction, mechanistic distinction.
Now, AUVELITY technically has SSRI plus NMDA. So the question is, do you think you would, however, get a black box for suicidal ideation due to the antidepressant?
Sure. That would, given we plan to file as an SNDA, an efficacy supplement, that means it would be under the brand name of AUVELITY. The label does have that warning as an antidepressant for suicidal ideation. You'd expect that to be present with respect to use as an antidepressant. Beyond that, it's.
Right, right, right. In terms of the marketing strategy, is there something you plan to do differently that REXULTI's doing right now?
I don't have specifics for you on, say, tactics, commercial tactics. I think we talked about a key element or a key differentiator, which is just the mechanistic or differentiation from the molecule. I think we also touched on some of the differences in the clinical data we have, both from an efficacy perspective and safety and tolerability perspective. I think those would ultimately flow into tactics. Yeah, we'll have more to say, but the team, the commercial team, medical affairs team, all that prep work is underway in anticipation of potential next steps for the program after a submission.
Okay. Then shifting gears, so that's on track for Q3.
Yep, yeah, on track.
Okay. Shifting gears to SYMBRAVO, which you mentioned earlier, you're launching imminently. We'll wait for that news. What can we expect on gross to net for this product for acute migraine? When I think about oral CGRPs, they may be pretty heavily discounted, and there may be heavy use of free drug. Would it be different for SYMBRAVO here?
Yeah, I think we'd expect some differences. You are right, migraine as a category is managed much differently, or payers manage it much differently from other categories. In terms of you'd expect just, or the way it's managed is, right, a PA to label, so confirmation of diagnosis, generally at least one generic triptan step and things like that. Free goods are a component of launches here. Sampling, that's a component, and we'd expect to have those. However, the way we'll be launching is a targeted effort, and we'll be focused on headache centers and headache specialists. There are about 150 headache centers in the U.S., the 100 reps that we talked about. That will be the area of focus. Of course, those centers and our initial prescriber target base, they write about two-thirds of the branded scripts for acute migraine treatments.
Many of those offices have the back office infrastructure and team to process PAs and support PA submissions. They're familiar with sampling. Many individuals who are being seen by a headache specialist have already tried multiple acute migraine treatments. That is where the initial focus will be, and then we'll go from there. Yep.
Okay. The positioning-wise, would this be used after a triptan, generic triptan, and then after a generic CGRP, or how are you positioning this drug?
Sure. The clinical data that we generated for SYMBRAVO, it's across a variety of migraine severities, which is great. That gives clinicians a variety of data points or data sets to make prescribing decisions. If you speak to KOLs, they indicate they're interested in potentially using the product in a number of patient profiles. If you step back, the reason for that is if you survey patients, there is still an overwhelming need, excuse me, in the market. There are a lot of treatment options, but patients are highly dissatisfied from an efficacy perspective. We're excited for the launch and the potential of the product. I think it's going to ultimately say towards steady state where the bulk of it of potential prescribing, I think we'll see.
That is ultimately going to depend on utilization management and where we net out from a coverage perspective. Our goal, of course, is to secure coverage early on and through steady state that would allow as many appropriate patients that a clinician or HCP wants to write for, that they are able to get the product that can.
One last question before we shift gears is shape of the curve with the launch in terms of the sales trajectory. Is it slow and steady or some kind of rapid adoption?
Sure. Scripts will be available, and folks can watch. We have not guided to that, but of course, we will be watching that internally, and others can as well. I think once we get off the launch pad, we will be able to comment on that with some type of informed commentary.
Sure, sure. Okay. Then shifting gears to reboxetine. I believe you're filing this NDA after the Alzheimer's agitation SNDA shortly thereafter, later this year.
We said, yeah, second half.
Second half, okay. Ultimately, can you also help us frame into context in the narcolepsy space where this would be positioned? When I think about narcolepsy, there are antidepressants, stimulants, oxybates, wake kicks. Where would this fit in?
Yeah. From a class or mechanistic perspective, it's a norepinephrine reuptake inhibitor. It's daytime dosing. We wouldn't expect scheduling. The initial focus, or we're planning for this to be for cataplexy in narcolepsy. Of course, we looked at other items across different studies in terms of impact of sleep or sleepiness and cognition. We like the other endpoints that we analyzed and the data that we saw. Yeah, it's an orphan indication. It's not ultra-orphan. There is a high need, and that can be with patients who may not tolerate, say, the bulk of currently available products or, say, just under penetration with respect to treatment options. We like the totality of the data and the overall product profile. We're definitely looking forward to that submission.
The work underway now is just the back office, the back office work of compiling the submission.
Okay. You have cataplexy data, so reducing attacks in NT1 narcolepsy. You mentioned you have data maybe on sleepiness. Have you shared that data, or when can we expect to?
We shared some of that data. For example, CONCERT, the phase II trial, we shared some data there. We have been presenting different data sets since the CONCERT study. Of course, the clinical work is done now. I do not think it should surprise you if you see additional presentations coming up. There are a number of conferences coming up, even ones in a few weeks. I think we will continue to present the data and just keep cracking away at the NDA submission and then go from there.
Okay, okay. And then one more product that could be approved in next year is esreboxetine, the right, yeah, reboxetine. But this time, that's for fibromyalgia pain. I believe you filed around first quarter. Maybe we're waiting for that acceptance any day now.
Yes.
Hence, it could be approved Q2 of next year maybe, or Q1.
Yeah, no, that's possible. I don't have, so right, next step is hearing for a potential acceptance decision of the NDA submission from FDA. If there should be an acceptance, then we would receive a potential PDUFA day that would allow us to comment. Yeah, you can do the math. We haven't shared the specifics yet, but I think your timing is, I'm sure you've got the parameters correct. Yeah, then share the next potential update for the program. If that's moving forward, launch work and the pre-commercial work, those gears have started turning as well.
If it is approved, why wouldn't someone want to use this product over existing drugs like Cymbalta or Lyrica?
Sure. The clinical data, compelling and with respect to pain and fibromyalgia. If you go, say, to FDA's Voice of the Patient report on fibromyalgia, a key burden and symptom for individuals with fibromyalgia is the fatigue. The product candidate, AXS-14, that did show, in effect, an impact on fatigue. That is important, and that is distinct from what is currently available as one example. We like the overall profile and the data that were generated, but we will see. Ultimately, detailing and if potential approval would ultimately depend on the label, but that is a key consideration is fatigue.
You mentioned you don't think reboxetine will be scheduled. Will esreboxetine be scheduled?
Yeah, we do not have an expectation of that either. Of course, mechanistically, they are the same, as you pointed out. Reboxetine is racemic, and esreboxetine is one of the stereoisomers. There is different selectivity associated with that. In terms of the AE profiles or things that might lead to scheduling, we do not have an expectation around that.
Okay, got it. Another question is, you got this compound from Pfizer four years ago. What exactly took you so long to file?
Sure. Yeah, no, part of it is just us running air traffic control on all the programs. We have a lot going on, which is great. It was us choreographing our work. With respect to 14 in particular, we are recapitulating the manufacturing process. You're right, Pfizer was the initial company that ran the clinical trials and did the manufacturing. That was discontinued. We had to go through the process for, as I mentioned, recapitulating the process and then putting up new stability batches, or registration batches, and then waiting for the stability data, etc. That work was underway, and that was rate limiting for the program.
Understood. In the last couple of minutes, maybe about your pipeline candidates, you have a whole bunch of phase III studies too as well. For the sake of this conversation, SUNOSI for ADHD, I would just love to know what makes you excited about this profile in this indication area, why it ultimately could be differentiated.
Yeah. I mean, there's ADHD, there's a high need, right? Stimulants, there's a non-stimulant available. The prevalence of the indication and then the impact to one's life is substantial. You have a variety of, depending on the individual and what they may have been prescribed, there are a variety of, say, tolerability questions or scheduling questions. On the other end of that spectrum, there are advocacy questions. There is a need. SUNOSI for solriamfetol for ADHD, the feedback, we were interested in that program initially because of feedback from KOLs and the mechanistic relevance, but also the feedback on, say, global changes for patients that have been prescribed the product, how they do. That's what led to wanting to actually explore solriamfetol in a number of additional indications.
ADHD, of course, that's a very, there's a large need. It's a large market. Yeah, we had the focus phase three trial that was in adults that read out earlier this year, positive trial, which is great. The next part of that program is the pediatric adolescent trial, which we need per FDA feedback to round out a potential NDA or SNDA package.
Okay. The last question in this program is then you're picking multiple doses for the pediatric or just one dose?
Oh, no, that's a great question. We haven't shared that yet. That I think you could probably, when we would comment on that, is, say, trial initiation. Right, that is a consideration. For the pediatric trials, typically that happens behind the scenes for programs as post-marketing commitments or requirements. Here, because of the indication, FDA requires it in advance. That is one of the considerations that goes into the study design.
Okay. That is all the time we have. Thank you so much for giving us an update about your programs and lots of things going on.
Thanks for having us, Andrew. Really appreciate it. Thanks.