Hey, thank you everyone for joining this year's Oppenheimer Healthcare Conference. My name is Frank Brisebois. I'm one of the senior analysts at the firm. Our next presenting company here is Aquestive Therapeutics. Aquestive is a company that we cover with an outperform rating. This is very exciting times for Aquestive. We've got a pivotal readout around the corner, in a field that's gaining a lot of traction here and interest. So with that, I won't go into the whole presentation just yet, but in terms of format, what we'll do is a fireside chat.
Feel free to send some questions. My email is francois.brisebois@opco.com. If not, I think in the Q&A chat I will get access to it. And so yeah, so thanks a lot, guys. We have the whole team here, joining. So maybe with that, I'll let you, you know, maybe give, for those that aren't aware of what's going on, Dan, maybe a quick overview of what you guys have been working on at Aquestive.
Yeah. No, and Frank, thank you for the invitation to be here today. We were here last year, and we enjoyed the conversation, and it's always good to be back. So thank you to you and the team at Oppenheimer. I think you said the right word, which is when I think about Aquestive right now and where we are, it's just exciting. We, when we were talking last year, we were really in this transformation or this, excuse me, this turnaround phase from a financial perspective, right?
And that was a multi-year process that we needed to get through, in order to get to a better place. But we don't spend our time right now, Steve, Carl, Ernie, and myself talking about turnaround. We're talking about transformation at this point. When we think about transformation, one of the first places you have to go in our company is our lead asset, of course, which is Anaphylm, epinephrine sublingual film, which will be indicated for the treatment of severe allergic reactions, including anaphylaxis.
If you, if you keep with that theme of transformation, and I'm sure we'll spend a good deal of time today talking about the anaphylaxis market, but we truly do believe this product has the potential to transform how patients are treated in the anaphylaxis space. Very excited about, about that. To, to answer your direct question, which was, you know, just a brief overview of the company, I would have people think of us in three different buckets.
First, these three buckets combined, I do believe, set us apart from our peers, or as I sometimes call it, our zip code. First, we are revenue generating. And, well, Ernie in a little while can talk about our, our revenue, but we through the third quarter where we've announced so far, we had good growth, and that's something that we want to continue. Second, we have not one, but two major assets that could launch in the next three years. The first one, Anaphylm, could launch as soon as 2025, and again, we'll talk a lot about that.
But the second one gets overlooked a lot, and that's Libervant diazepam buccal film, which is indicated for the treatment of seizure clusters in patients diagnosed with epilepsy. That product already has a tentative approval with the FDA. The adult application can launch in 2027, so under three years. We actually have a PDUFA date in the next several months, in the next two months, on a 2- 5 year old patient application, which could get us in the market as soon as this summer.
Then the third part of our platform, I would point out to everyone, is we do have the technology in-house to refill our pipeline when both Libervant and Anaphylm graduate into that commercial realm. So when I look at our company and I see revenue, two products that are near-term to market, and the ability to backfill our pipeline, to me, that is exciting and transformational.
Okay. Great. Yeah. No, when I looked at the company, at that time, it was very much a turnaround story, but there is a full-blown company going on with a lot of different assets, a growing kind of revenue stream, and a lot in the pipeline, which, you know, most of it wasn't really accounted for anymore. So, so great work on getting everything figured out, getting the balance sheet figured out.
And maybe, you know, this is an awkward timing for it, and I usually wouldn't do this, but it's been such a big part of the story. Ernie, maybe can you help us understand a little bit what you've done with the debt, the restructuring, and where you stand right now in terms of the, the balance sheet?
Sure, Frank. And again, it's a pleasure to be here. We last year, as Dan mentioned, was a transformational year. And really, in the fourth quarter, we were able to refinance our existing outstanding debt that had entered the principal amortization stage. So it was consuming precious cash as we were looking to move forward on the Anaphylm program. So we were able to refinance that back to an interest-only period that would save us over, or approximately $30 million that was due over the next 18 months at a very pivotal time in the development of Anaphylm.
So we've taken care of that. You know, I might also add that, you know, last year, our guidance, we were able to improve our guidance every quarter, to where it is now of revenue of $47 million-$50 million and an EBITDA loss of $14 million-$17 million. So it showed progress through the year, as Dan said, of the strength of the underlying business as well as the, you know, as we continue to fund the development of the two products and, you know, the upside that might be there.
Okay. Helpful. Then, so in terms of clinical, upcoming clinical and regulatory milestones, Dan, where, where do we stand here? We have data, very close, in terms of Anaphylm, but from there, where, where do we go here? And just maybe give us an idea of in that data release, that you're expecting this quarter, what goes into that? Is there anything about the regulatory side? Is it single dose, repeat dose? Is it all in one package? What, what should we be expecting here?
Yeah. Well, I'll lay out the timeline for you, and then I'll hand it over to Carl, who can talk about the study design and what we actually we'll see in terms of data, obviously not the results, but what we expect. We'll have our pivotal study, full pivotal study readout in March. We'll also at that time have our FDA meeting minutes from our Type C FDA meeting that is in Q1. When we look at the rest of the year, the next milestone would be a pre-NDA meeting with the FDA, which we expect to be in the second half of the year.
And then we remain on track to file our application by the end of the year, which with a 10-month review cycle would put us in the market in the second half of 2025. So I'll let Carl expound upon, expand upon, excuse me, the actual design of the pivotal study.
Yeah. No, thanks, Dan. And, Frank, to be more specific, this is a 505(b)(2) submission. So one of the critical events for us is to demonstrate that we have appropriate comparability and sustainability of our pharmacokinetics using our Anaphylm compared to reference-listed drugs, as well as published thresholds that would be appropriate to meet for the indication of anaphylactic reactions.
So the way the program has been designed for our pivotal study is to address and evaluate single dose, ensuring that we have appropriate comparability by virtue of partial AUCs, and then also evaluating sustainability over particular thresholds as well as comparison to reference-listed drugs. Those are single doses. And we also have included in the program a repeat dose as well to address sustainability.
Okay. Perfect. And then, in terms of the data to date, you know, I tell people it's a fairly simple story. At the same time, the precedence is a little tricky in terms of the clarity of how EpiPen got to market and the trials that are necessary. So what would you, if you were to guide investors as to the most important data to date that's been shown, point people to?
Well, I do want Carl to give his thoughts in a second, but I can't help but give you three things to think about at a very high level. First, in that critical early time period, we believe we are comparable to the autoinjector. So not the manual IM, but the autoinjector. Second, when you look at the pharmacodynamic measurements, which Carl and other physicians look at in terms of what's happening in the body, at 2 minutes, the change from baseline that we see is greater than the autoinjectors.
And three, the peak time, so our TMAX, the time to maximum concentration of our product, is consistently in our studies between 8-15 minutes. So an average of 12, call it across the board, that puts us right on line once again with the autoinjectors. But I'll let Carl give his view as well.
You know, I mean, I think Dan summarized that exactly, spot on. I view the program to date as reflective, at least the 301 study or pivotal trial is a confirmatory study of what we've already demonstrated in 103. So we already have our baseline data set demonstrating comparability. We've just expanded the population and included the necessary metrics to meet the pivotal status. So I think there's good pretest suspicion and likelihood of achieving those metrics based on the 103 data set to date.
Okay. And it is an interesting study design where, you know, you're not going to give people anaphylaxis and then test the product. So PK/PD comes up a ton when we've heard a competitor's AdCom. You know, can you remind us of what is mostly shown? Maybe what's more important to you in the clinical setting, PK or PD, and what seems to be more important to the FDA here?
Carl, do you want to take that one?
Yeah. No, happy to. Look, from my perspective, as a clinician, understanding that what we give patients is having a demonstrable effect on them is what's most important. So seeing quickly a change in vital signs, systolic blood pressure, heart rate, are, I think, really good measures to know that the drug is doing something and it's working.
As far as the FDA is concerned, they also want to make sure that the pharmacokinetics align with what they're targeting from the perspective of a 505(b)(2) submission. So I think given those two and what we've heard at the AdC om from last year, it's the totality of those data elements that will roll up into the overall evaluation and submission of our NDA.
Okay. And so off of that, after the AdC om, this is a competitor story, which is a nasal spray, kind of, epinephrine here. But can you remind us what the CRL was about here in their situation?
Well, we can obviously share what we've heard publicly, which is the same as probably everyone else. Publicly, what we've heard is they received a CRL that talked to their allergic rhinitis study where they had done one dose and did not do a repeat dose. During the AdC om that they had with the FDA, the FDA presented the slide of that data, which showed a rapid peak, a lower peak, and a rapid decline starting at 10 minutes. So my understanding from what has been said publicly is the FDA was concerned by that and said, "We'd like to see what a repeat dose looked like, to see if that's sufficient in cases where people are congested.
Congestion. So for people to understand, rhinitis is just nasal congestion, right? And so, you know, if you translate that potential concern here to your story, would edema be the parallel here or the kind of it's just it's hard for me to fully understand because to me, the prevalence or whatnot of edema versus congestion is a lot more rare. And so if that is the case, what have you guys done or prepared to feel comfortable that that issue with the nasal spray probably shouldn't repeat itself with you guys?
Sure. Yeah. I would take it up one level, perhaps, is the way to put it. I think the parallel to us and anyone else coming into this space is the FDA is going to do their job, right? They're going to make sure that under whatever conditions they can think of, that the product works in a way that they're comfortable, will be safe and efficacious. So for nasal sprays, obviously, congestion is something that is common in everyday life, and that becomes a concern. We don't think that plays in our technology at all, and Carl and Steve can talk to it if necessary.
In terms of edema, I think edema is something that will be, was appears to have been looked at in the nasal spray programs, and of course, will be in ours as well. In the Type C meeting that will happen this quarter, Carl and the team will be talking with the FDA on our plan to show what our data looks like if there is potential edema. And we feel confident that we can run a study that is sufficient for the FDA to get comfortable with any concerns they may have on that front.
Okay. Great. And, sorry, was someone else going to comment on that or? Okay. Just so, you know, now that that's a little bit out of the way here, I think the discussion turns into the commercial opportunity here. And so, you know, EpiPen seems to work. It's obviously been around for a long time now. Are people taking it on time? Are they carrying it? Are they refilling it? Is a whole different discussion. But if someone was to say, what is the actual unmet need here for patients? Is it clear or does this require education here?
Yeah. I think it's really clear. And I actually think that may be a spot that anyone coming into this space will agree on. By far the biggest issue in this space is people don't carry their product. They do not carry the rescue medical device. And there are study after study which shows the rates are 40%, 50%, 60% of the time, people do not have the product with them when they need it. And the second big problem in this space is even when they have it with them, they wait to use it. So, you could call it the I'm fine syndrome, right?
You're exposed to something, you start to feel a little scratchiness. I'm fine. I'm going to wait. You wait till it progresses. I'm fine. I'm going to wait. You take a Benadryl. You wait. And then finally, you're in this moment of crisis and you now you need to be rescued, right? So when we look at our product, and this is my favorite part of these talks, I get to show you the product. When we look at our product, we think we can affect the carry rate quite a bit. And we call it bending the carry curve, right? Because I actually carry this is my phone. I actually carry two Anaphylm placebos on the back of my phone at all times.
And it's not even the magnetic case that you attach to your phone. It literally is just inside of the case. And we think that's meaningful because 97% of Americans have a smartphone. And if they're like me, I have it with me all of the time. So I'm just going to pull it out and I'll show you what the—you got to put it in front of my body, I guess—show you what the film actually looks like. And the really cool thing about this, and I have to give credit to Steve and his team, is you can submerge this in water. You can freeze it. You can have it in heat. You could run it over with your car and it will still work. So it's a lot more durable than even the phone you're going to carry it in.
How many come in one? Is it one per package and you just carry two? Is that fair?
Well, the EpiPen script right now is two because there are instances where you need a second one, at this time. And Carl, jump in if you want to add to this. At this time, we don't see doing anything different.
Okay .
And then, it's interesting because the speed of onset seems to be such a big deal when you listen to the AdC om as it should be, right? You want this to act quickly. But what's interesting is the, you know, the willingness to try a needle versus something else like a film. It's almost like the speed of onset should be, you know, triggered once the panic starts.
You know, I'm okay. I'm okay. I'm okay. And then you go, well, you're already 15 minutes into it, right? So it's a kind of a, but I don't know if we'll ever get to that stage, but I sure it makes sense to think someone would wait as long as possible before you take the needle or inject, you know, any, anyone around you. So, okay.
It's natural with a rescue device, right, to want to wait because it's in the word rescue device, right?
Right.
If you look at the actual label, the label is for the treatment of severe allergic reaction, including anaphylaxis. So it's that whole timeframe. And we believe an oral product, just like Benadryl is used today, will be used earlier in the cycle.
If someone was to say, well, yeah, okay, fine, but you know how it works. If you're trying to come out with a branded, generics are tough to beat, and you know, step edits or whatnot. But in this case, what happened to the pricing branded versus generic? Is it fair to say the generic is still not that different or?
My understanding of the pricing of autoinjectors is the generic is about half the price of the branded. But the entire market at this point for autoinjectors is basically generic. I believe it's like 95% of scripts. So from a pricing standpoint, I guess the way you could call it, the market really is at the auto, the generic autoinjector price.
Okay. And if you were to look at kind of the size, the competition here, I guess we talked about a little bit, but just the dynamics, what are you going to come in and, you know, I would say you're a little bit time-wise behind the nasal, based on just what it seems like. You know, you still have to read out your data. How do you, do you, you know, do you hope for the nasals to come in? How do you compare yourself to the market if they come in or if they don't? Does it even matter? How do you fit in the market here?
Yeah. For us, I think maybe the right way to put it is I think we win either way, right? It's this is not a sprint of just a year or two years. This is a decade or more of time in the market, right? So if the nasal sprays do get to the market ahead of us, great. They're going to help with expanding the market and making sure people understand the need to move away from needles. That's helpful. If they don't come to the market, we'll have to do that lift on our own. But then we'll obviously be the first to market. So either way, I think there are good things for our company, especially where we are right now.
Where is the market, you know, people that carry EpiPen right now, or is it just patients at risk? Like, how do you gauge how big this market actually is? At its peak, what do we, what do we know about how big EpiPen got?
Yeah. I think, well, I'll answer the last question first. The EpiPen market in terms of scripts is as large right now as it's ever been. So it's around 5 million scripts a year. But like most markets, when you look at the prevalence rate or the at-risk rate, it is much higher. So if you figure that 5 million scripts a year equates to 5 million people, there's something like 17 million people in this country who will experience anaphylaxis or a severe allergic reaction in their lifetime. And if you go to just those who have diagnosed allergies and should have a rescue plan, that number is even larger.
And some would say it's like 40 million. So, there's definitely room to expand the market. Obviously the first place to spend time is with the people who are currently at least getting a prescription for an EpiPen but apparently not carrying it.
Do you think, and sorry, this is a little off the cuff, but it's just, it's such a real-world problem where everyone knows what the EpiPen is, right? And so would you ever expect people to fear, you know, schools, you know, kind of nurses or whoever at the health center say, "Look, I'm going to try the film, but I'm going to have an EpiPen as my backup just in case because I feel more comfortable"? Is that something that you'd have to progress through, or do you expect there's no reason to think that the EpiPen would be safer as a rescue?
Well, we can go into the science and clinical side, to the extent you want to. From our perspective and the data we're collecting and the label we will have, there's no reason to carry an EpiPen. There is no reason to have a backup, with our product. Having said that, we get that the EpiPen product has been on the market for 30 years or something, like that. So we understand that there will be a group of people that will take time to become comfortable with it. It's like any product, right? You'll have your early movers. You'll have the people who are wait and see. So you just have to work through that.
Yep. And then, in terms of the IP, where, where do we stand here?
Well, I'll let Steve take that one.
Thanks. Yeah. So we have intellectual property around this. The prodrug is something we developed in-house. And we have intellectual property in development around the composition, the molecule, all those features, and should reach out into the 2040s.
Okay. Okay. So plenty of time. And then I've got a kind of a different question here to move from Anaphylm, which used to be the AQST-109, I believe. You guys used to talk about 108. And as a topical cream formulation, this is a little different from the other kind of sublingual, buccal film that you have. So, where does that stand and what's the opportunity here with 108?
Yeah. And I'll, I'll turn it over to Steve in a second who can talk about, we're a little hamstrung by what we've said publicly, but he can talk a little bit about what his thoughts are in this area. But what gets me excited, and I talked at the beginning about this idea of transformation, is 108 is actually one of the original prodrugs that we looked at for the anaphylaxis indication. But the problem with 108 is it was too slow to convert, right?
So Steve and Carl and the great team we have have spent a lot of time thinking about where that could be put to work. And when you go to dermatology, there's a lot of places we believe that that can be put to work. So, before I go farther, I'll let Steve give his thoughts.
Thanks. Yeah. Well, you know, epinephrine works with adrenergic receptors. And, as we know, it's well documented throughout its use in for anaphylaxis. And from a dermatological perspective, you get under the skin, there's a wide variety of indications that are impacted by the mast cells and the various factors within there.
And epinephrine, of course, while present endogenously, doesn't permeate well and is cleared rapidly from the site when it was explored in the early days. So, you know, there's a lot of excitement that we can introduce epinephrine there and utilize its action in a meaningful way. And we're continuing to explore what exactly those indications may be.
Okay. Okay. That's great. And then, you know, on the Libervant side, you had mentioned you have that age group of younger, age group that, you have the Valtoco coming up here. But as a whole, I think, you know, scary to say we're already in 2024. When does the ODE block end for Libervant as a, as a whole here?
Well, if I had to give an exact date, I'd say January 11th, 2027.
Okay. If you had to. Okay.
I had to.
So that's a wild guess. So 2027, which, you know, ultimately, and you, you could be, I think you mentioned on the market here, second half 2025 with Anaphylm is a possibility. So then you have 2026 and 2027 is, you know, that's pretty early in 2027, January. So I think that's the side of, of the business that, it's still very much there. And so can you just remind us a little bit maybe on Libervant what that opportunity is? Is it meaningful, or is this just kind of a, you know, a part of the pipeline that, that is less important?
Yeah. No, it's definitely very meaningful. As far as we can tell from the data that you can buy places like Symphony, in 2023, the overall seizure cluster market was north of $250 million. And right now, that's divided between three medical devices, right? So we do believe an oral buccal film offers patients additional choice and could be very impactful in that space, especially since 60% of the patients in this particular indication have an aura before their seizure starts, right?
So they have the ability to treat in terms of the two- to five-year-old space, that's obviously just a subcomponent of it. But what we would like to do, because we don't think focusing on launching Anaphylm and Libervant is a good idea, is we would like to find the right partner to launch Libervant for us, as we get past our PDUFA date.
That work is obviously been ongoing for some time. We're continuing to be there, as we've said we would be. We will continue to make sure we find the right partnership and it's the right sharing arrangement. But we do believe that will, that will be something you see in the future.
How, how does a company your size believe that, you know, Anaphylm, you can, are you, do you think you can give this a shot yourself, or is this a partnering as well? How, how much of a push is this? It seems like a very, very big patient population.
Sure. Yeah. I should do my job and be very clear on this point. We absolutely can launch this product. There's no doubt that we have the ability to launch this product. When you look at the space, and we, there's plenty of analogs to look at as well, right? You have Auvi-Q has a sales force of, I don't know, 60-ish people. I think at its peak, Mylan with epinephrine had less than 200 sales reps. So you're talking about if you just use the mid-range, somewhere around 100 sales reps.
That is not a gigantic sales force, right? The other thing that people sometimes forget is, yes, scripts are spread across a wide variety of call points, but half of the scripts are with allergists and pediatricians, which are both fairly concentrated call points. So yes, we do believe that we, just like we did several years ago in the epilepsy space, we do believe we can launch effectively and within our means.
Okay. Okay. I think we're coming up on time here. So, anything that, that we missed, you know, very important times here for the company, anything that you want to mention as we, as we close out?
No, I think you were very thorough. I just want to make sure that people understand how excited we are about where we are and where we're going. And we appreciate the time.
March is getting close, so.
March is getting close.
Great time. Okay. All right, guys. Thank you very much. Hopefully, this was helpful to everyone viewing the call as well. Thank you.
Thank you.