Okay, great. Thank you very much for joining today. My name is François Brisebois. I'm one of the Biotech Analysts at Oppenheimer. Our next presenting company here is Aquestive Therapeutics. From the company, we have a whole group of people, so I'll let you look at the screen and figure out who you have, and with that, you know, thanks for joining. In terms of format, this will just be a fireside chat. If you have any questions, you can send them in the Q&A tab at the bottom of the screen. You can also email me. It's that name you see there with the dot in the middle at opco.com. So with that, thank you for joining. Dan, maybe just an update on, you know, what's going on with Aquestive and why this is a very important time for the company.
Sure. And François , as always, thank you for the invitation to present today and for the invitation to be a part of your conference. We always enjoy these engagements. And just for those who are watching today, I'm pleased to be joined by my colleagues, Ernie Toth, our CFO, Sherry Korczynski, our SVP of Commercial, and Steve Wargacki, our Chief Science Officer. So, as François you said, we have the whole crew here, right? As I was thinking about today's conversation, I hadn't really realized that the last time I said anything publicly was about 90 days ago at our Q3 earnings call in November so and that's a long time for us. We typically have different spots along the way where we've spoken publicly.
I wanted to make sure that I'm really clear with everyone today on where we are and how we're feeling since 90 days has gone by. And I will tell you, I feel fantastic. I'm very excited about where this company is right now. We're on the cusp of filing our NDA for our lead asset, Anaphylm, which is an epinephrine film sublingually administered, excuse me, for anaphylaxis. We are finishing up our pediatric study, which is what will go into that NDA. We had a very positive interaction with the FDA in November in a pre-NDA setting for Anaphylm, so we feel very good about the engagement with the FDA. On our other programs, AQST-108, which is our epinephrine topical gel for alopecia areata , we had a very positive pre-IND engagement with the FDA in December.
Our base business is humming along just like we expected it to and remains healthy. We announced last month that we ended the year with $71 million in cash. Sitting here today, I feel very happy with what the company has done and also where we're going.
Excellent. Okay, so on track, I was thinking the same thing. I was looking up the website, and you're right, since third quarter or nothing, which is in this space, could be a long time. So just in terms of the filing, you talked about the pediatric study. Is that all that's left? Like, what remains to be done before filing it?
Yeah, no, I'm actually in our office in New Jersey, which is where our headquarters are, and around me are a variety of people who are writing as we speak the sections of the NDA. So for those of you familiar with the modules, Steve and his team, who are responsible for the CMC and product sections, that work's all done, right? That's ready to go and in great shape. And what we're working on now is making sure that the clinical story, all the pieces and parts of the Module 2 clinical piece, are put together in the best way possible. So that's the work that's going on right now. As I mentioned before, there is a small pediatric study, a single dose study in 18-24 subjects that we're running right now. We'll wrap that up in the coming weeks.
And the data that will go into the NDA from that will be obviously the safety data. And there will also be a couple of PK charts that will get included as well.
Okay, great. And then in terms of the FDA, you know, there's been an AdCom for a competitor. You guys have had a lot of discussions with the FDA. Where do you think the focus of the review should be here?
Sure. So one of the things I'll actually say I'm proud of this, but I'm not sure that it's whether it's helped the company or hurt the company, but I'm proud of how transparent we are. So in our pre-NDA meeting, we provided everyone with pretty much verbatim what we got back from the FDA. And we've tried to do that all along. So in our case, we believe it's very clear the two areas that the FDA will want to talk to us on. And if you think about our package, we're using what's called the 505(b)(2) filing route, which means we're comparing ourselves to another existing product using pharmacokinetics and pharmacodynamics. So in doing that, where you get questions from the FDA is any time that you are different than that comparator.
There's two spots where our data does differ and needs explanation in order to be understood, right? The first is when we give a second dose, so in this disease state, the first dose is by and large what works, but there's a second dose that is sometimes administered. When we give a second dose, we do see a subgroup of subjects who for a transient period of time, five or 10 minutes, have higher levels of epinephrine than the known levels with the EpiPen autoinjector. So we can't rely on the safety package from EpiPen for that. We have to explain it to the FDA, right? And I'm happy to go into that in a minute for you if you'd like. And the second area is out at 45 minutes after administration, our geometric mean value of our blood levels go below those of the manual injection.
So we're out of bracket is the term people will use at 45 to 60 minutes. So that's another spot that we're different and we have to explain to the FDA.
Okay. So.
You want me to dig in a little deeper?
Yeah, that's where all of the questions, most, I mean, then there's commercial, which is a big, big part of it. But, you know, we can't get to commercial if this doesn't get through. So for this one, this is the big one. So on the safety, we've done our work, we have our opinions, but I'd love to hear your comfort on both.
Yeah, and one of the things we have to figure out as a company, we do need to share more information here, show more data to everyone, because I think we obviously have the benefit of having all the data, and so we're very comfortable. People outside of our four walls don't necessarily have all of that data. So let's talk about it a little bit more, right? In the literature that's available, where studies have been done by other people, it clearly shows that if you give a robust level of epinephrine, the odds of needing a second dose go way down. So even without that data, only about 7%-13% of subjects or patients will take a second dose. And if you get a robust amount in your first dose, that'll be even significantly lower than that, right?
One of the nice things about our product is you do get a robust dose with your first. You get a robust level with your first dose. What we've done is we looked at our repeat dose data and we divided it into two subgroups, right? One, the subgroup that got a robust dose. And by and large, not even by and large, actually completely, that's the group that has the high epinephrine levels for a transient period of time. So that group in a real-world setting would only have taken a second dose if they were not following directions or were overly anxious or had done something they didn't need to do. They don't need a second dose, right? Now there's a subgroup that had lower levels of epinephrine, and you could argue maybe in a real-world setting, they would have needed a second dose.
When we take that subgroup and we compare it to the same subgroup with the autoinjector, there are no outliers. Our Cmaxs are on top of each other. So if you think about the individuals who do need a second dose with our product compared to the individuals with the autoinjector who need a second dose, there is no issue. So what we'll show the FDA is that when you force us to give everyone a second dose, yeah, there are some people who are going to get higher levels than they need. But when you think about it in the way it's going to work in the real world, we actually do not have the issue that has been raised.
Anaphylaxis, you know, like it's very serious, but the amount of people that actually have, you know, fatal consequences is very low, right? And so if you're looking at visits, do those levels worry docs in terms of the Cmax levels? Because it seems like if it's transient, these aren't levels that are extremely worrisome anyways. Is that fair or?
Yeah, with the medical experts we've talked to, not even a little bit.
Yeah.
So why is that? Well, one, they've seen much higher levels than what we're giving. And two, when you look at our AE data, it's very clean. So in that group where they had a transient high level for five or ten minutes, we don't have an AE signal of any kind.
Okay, it seems undeniable, rational, logical. It seems to make a ton of sense that you want it to be the speed of onset is the game here. Not only taking the medicine, but it actually working fast, which in the real world, everyone kind of understands that people are very slow to inject, but can you talk about that second part of it on the durability side, whether or not it matters as much, and just kind of talk about that PK curve?
Yeah.
45 minutes.
And François , if you're okay, just one last comment on the high levels. We do feel like there's a little bit of needing to, I'll call it flip the script a little bit, right? How is it in a rescue medication that the concern is, "Oh my God, did you give too much?" as opposed to, "Oh my God, did you give too little?" Right? If you line 100 people up, tell them they're going to have an allergic reaction, say this drug is going to help you, do you think their first question is going to be, "But are you going to give me too much?" Or is their first question going to be, "But is it going to work? Am I going to get enough?" Right? So.
In the situation where you really need to make sure you get enough.
What is too much? No one has any idea what too much is, but I know it's much higher than what we're giving.
Okay. Yep.
So the second issue that we talked about is this idea of bracketing, right? The FDA classically looks at 505(b)(2)s. One, they look at your Cmax. And two, they look at something called partial AUC, right? The amount of drug that you're giving over a period of time. From a partial AUC perspective, we are bracketed out to 60 minutes. In some of our studies, if you look at the individual time points around 45 minutes, 50, 55, 60 minutes, we are those individual time points on a geometric mean basis are lower than the comparator products. That's what the sustainability comment has been that we have talked about. The first thing to realize is when we talk to our medical experts, nobody can tell us why this would be important. You're 45 minutes out from when you dosed yourself to take care of a rescue situation.
If at 45 minutes, the product hasn't worked, you've long ago taken a second dose, right? So we think there's a little bit of a nonsensical component to this. The other thing, and Steve loves to champion this argument with me, if you look at the manual injection, it has a very slow uptake and then starts to ramp, right? So again, if you're someone who's having an allergic reaction, which product do you want? The one that's really slow and then eventually goes up, or the one that right away gives you a high level of epinephrine to stop the reaction? So we feel very comfortable that this issue is one that we can align with on the FDA. One last point that's probably important from a kind of check-the-box standpoint.
When you break apart the data points at 45 minutes, ours versus the EpiPen, while our geometric mean may be below theirs, we are inside of their data set. So if you think of all the dots of all the individuals, we don't have dots that are higher or lower than the EpiPen. So we think that's also a compelling way for the FDA to think about it.
Yeah. Sorry, I don't know if Steve was going to jump in. I'll get him. Okay, perfect. Okay, well, on that side, I think that's good. And then I think it's impossible to, you know, obviously there's an AdCom that was a fun one to watch or listen to. And, you know, an ultimate outcome of a launch here from a competitor product, you know, that's nasal. I'd love to hear just any comments you have on the launch so far and, you know, any thoughts about them at all would be.
Yeah, happy to. Well, look, we obviously, like any competitor, we've been watching what's been going on in the public domain. And as far as I can see, there's three things that our competitor is focused on. And this is from their words and also what they've published. One is awareness, right? They're spending a lot of money, a lot of time on making everyone aware that there's an alternative product to the needle autoinjector that exists. Love it. We hope they spend all kinds of money on awareness because that helps everybody. So from an awareness perspective, they've got a long way to go, and we expect them to continue to spend in a major way in that area. The second place that we see them spending a lot of time is on coverage.
Market access and coverage is obviously an area that is painful for any life sciences company. There's just no quick answer no matter who you are, even if you're Pfizer or one of the big guys, right, so from our perspective, we continue to learn from how they are interacting, and what we've done to make sure we're ready is we've actually, Sherry has actually brought in market access talent into our company, and we're engaging now with the market access individual, the payers, to make sure they understand who we are and that we're coming, and then the third place, which I was interested to see, I'll call it, that ARS has put into its deck is that they have physicians who want to understand clinical efficacy better before prescribing the product.
We've actually seen this in some posts as well just by physicians around the country of, "Hey, I'm going to let that guy over there try it first, and then I'll give it to my patients," right? From an Aquestive perspective, what I think that means is we'll definitely want to leverage our OAS study, right? Our Oral Allergy Syndrome challenge study, excuse me, because that's a study where we exposed people to an allergen, allowed symptoms to develop, including edema, and then dosed our product to show how quickly relief occurred. We think for physicians who are worried about clinical efficacy, that's a really nice set of data for us to be able to share with them when the time comes.
But no one else has that kind of efficacy data.
As far as I'm aware, we are the only one who have data such like that.
That's interesting. And okay, so have you heard from, I don't know if it's schools or who, and we can get into the commercial who the accounts are, but have you heard of people, you know, for years from the start to kind of say, "Look, we'll take neffy or we'll take a new," everyone gets it that, you know, something that's non-injectable is great, but we're going to keep the EpiPen for that second dose just in case I feel less liable or whatever the reason is to use the EpiPen on the second dose, or is it like once they kind of switch, they switch?
I think this is a big enough market that you're going to find a little bit of everything. We have not seen that as a prevalent theme that has been told to us about our competitor's product or our product. But I'm sure it exists. I think what we've tried to stay focused on, and maybe Sherry, this is a good place for you to just give your view, but we've tried to stay focused on what is it that the patients want and need.
Yeah, so I'm happy to jump in here. From a commercial perspective, we have, and you know that I've been in this space for quite a long time, having worked on the EpiPen brand for many years. And, you know, continually patients have said they want something that's easy to carry, easy to use, and it works quickly. And so I think that at the end of the day, when you stack everything up, Anaphylm is the only product that will really meet those needs. And I know we've shown you how easy it is to carry actually on the back of the phone. And so when time is of the essence in an allergic emergency, you want patients to be able to readily access and feel confident in using their medication correctly.
And so again, I feel very strongly, we feel very strongly that we've built, as I like to say, the holy grail of epinephrine, and that this is a product that people will have on them kind of as an extension of themselves and be able to use quickly. And even if there's one death associated with not using the epinephrine quick enough, that's one too many in my mind. And so when we have a product that can be easily accessed, I mean, within seconds, and to be used and works and works quickly, we feel very strongly about that. We have been conducting, as you would imagine, plenty of market research. We are progressing nicely on our launch plan. Everything is on track, as you would expect, HCP messaging, consumer messaging. Obviously, patients and their caregivers have a big say in the medication they take in this space.
And so we feel strongly the importance of being able to effectively communicate with this patient group. As Dan mentioned too, we have been working with the payers since last fall so that they're aware that Anaphylm is coming and to prepare for that. And we have hired a highly, highly experienced market access woman, and she will be starting with us very shortly, but she's highly experienced in launching big and small brands. And so we're excited to have her on board. So at the end of the day, you know, we are on track from a commercial perspective. We know what has to be done and when it needs to be done by. And, you know, hopefully this year, this time next year, patients will have a new choice.
Yeah, no, that's great. And maybe Sherry, because you brought this up a little bit, and I think it's important for listeners to know this. Can you just help us maybe understand a little bit more your background with EpiPen?
Oh, yeah, sure. I would be happy to. I spent about eight years at Mylan, and while I was at Mylan, I had experienced everything from advocacy to public relations, government affairs, and ultimately I led the entire EpiPen brand. We took it from about $150 million to over $1 billion with strong messaging, sales, and consumer DTC work.
So on that note, I mean, because it's so intuitive on the DTC, there's certain stories and I covered biotech and a lot of them are not intuitive. But this one is hard to deny. You explained this very quick to someone. I called it EpiPen as a Listerine.
Yeah, thin strip.
Too many times. But is that something that we want the launch to get going first or, you know, it's like a progressive kind of thing? And once we hit a certain level, we can maybe think of DTC? Or is this, if, you know, hopefully this gets approved and then we start really ramping up on this?
Yeah, I think it's all, you know, you look at it in tranches, right? I mean, obviously the payers are critical and we start to work on them. We start to work on them already, but those contracts don't get signed. You know, that'll take a little bit of time. And I do believe the HCP messaging first and foremost, the physician has to believe in the med. Dan talked about this, showing our efficacy. It's going to be great that we have the OAS data, but really ensuring they feel comfortable with prescribing the product and making consumers aware. So I think you'll see the same sorts of things with us is the advocacy groups and the advocacy associations pushing out messaging, beginning advertising, journals, magazines.
I think from a big-time spend, if you will, TV ads, those sorts of things, that will obviously you will ramp up with that over time. I don't think that's something you would see in the first kind of nine to twelve months.
Understood and then, yeah, on the, you know, the convenience side of something easy to carry that you mentioned, you know, and epinephrine is such a difficult molecule, the variability is out of control. But when I've spoken to doctors, and you don't need to be a doctor to understand this, but even, you know, you go past the injector, to me having two nasal sprays and we know the kind of bottle that they come in versus this, I mean, if you're going convenience, it's impossible to not think that this behind your phone is probably more convenient, right?
I think that's where it's just. I think people try to nitpick everything, but ultimately that's what's happened to me where I've tried to nitpick this data so much and then ultimately it comes into even the doctors kind of looked at me, they go, "Stop trying to nitpick it. We struggle with this molecule. This is the most convenient thing we've ever seen.
That's great to hear. That's very consistent with our market research. When given the option, physicians and caregivers, patients alike choose Anaphylm for that very reason. It is so easy to carry and very easy to use.
I don't think this is the best place to get political, but any impact with what's going on in government from your guys' perspective being that you're so close to that stage of your company?
Yeah, you know, François , I actually didn't do my job and I'm surprised, Sherry, you didn't call me out on it, but I showed the product while she was talking. So if you can see the back of my phone, see the yellow, that's actually our product on the back of a phone. But yeah, fair point, not getting political, right? What we've seen inside of the FDA is the reviewer group that we're dealing with for Anaphylm, which is the same reviewer group that reviewed neffy. We've dealt with the same people all along. All of them are still there. The engagement remains the same. So while at the broader levels of government, there's obviously massive changes that are going on for a variety of reasons, in our little slice of the universe, things appear to be very stable right now.
Okay. I'm sorry we took so much time on 109, but Anaphylm, I don't think we, I think we had to, but 108, I'd like to hear just maybe what investors should be looking out for in 2025.
Yeah, and I'll kick it over to Steve because this is once again one of his great ideas. But from a market perspective, alopecia areata we think is ripe for innovation, right? Right now, JAK inhibitors dominate the space. They have a black box warning. It's a systemic delivery of a large molecule. It's very expensive. And we believe epinephrine in a local gel form can be equal to or better than those products. And so Steve, maybe we could talk a little bit about what the next steps are for that program.
Sure. Yeah. So as you mentioned, we did have our pre-IND interaction with the agency. And so we're in the stages right now, besides filing the Anaphylm NDA, opening up our IND and getting ready to start our phase II-A study. That's going to be a typical II-A study. It's, you know, 24-ish to 48 subjects. It's going to be, it's alopecia, so it's going to be the 12- to 24-week kind of time span. And we're going to look at SALT scores, growth from hair, measure by a variety of metrics there, look for any, you know, biomarkers or photography we can utilize, and explore some doses, concentrations, and dosing regimens. All the things you'd expect to do at this early phase, but it's a really exciting step for this program.
Why does AQST-108 mechanistically make sense here for AA?
Sure. Well, epinephrine is an immunomodulator and your body's been doing it for a very long time. But what we have through the Adrenoverse is the ability to control the delivery of epinephrine and the concentration, the duration of epinephrine locally, which will allow us to, as we demonstrated through our non-clinical program, control the cytokines, interact with NK cells, and do all the things at a local environment upstream from the cascade of what may happen with the JAKs inhibitors or other therapies, but controlling it at that site. But the action of epinephrine has been well known in our bodies, at least for a very long time.
And the delivery secret. Good stuff. So I think we're coming up on the end of it. Is there anything I should have asked? There's a lot going on. Ernie, I'm sorry. Dan already said $71 million. How do we feel about that? What do we do with that? Maybe, yeah, I'll put you on the spot.
Sure. I think we did announce that we had over $71 million of cash and that gets us through this year, gets us through the FDA process with the filing and if we have an AdCom and through hopefully an approval. It also supports Sherry in all of her pre-commercial activities this year to make sure that we're prepared for a potential launch next year. But what we should remember is we do have a variety of levers that we pull. We still have Libervant that we could out-license if we chose to. We still have all the rights to Anaphylm. So if we thought it would be better off in an ex-US with another partner, we have those options. And we still have other, you know, we have the ability probably to raise debt should we choose to go that route for non-dilutive financing.
So I think it's important with the cash we have on hand and our existing business and some of the other things that we have that we feel good about where we're at from a cash perspective.
Anything we missed, Dan?
François , as always, you're very thorough, so we appreciate the questions going around the parts of our business and really enjoyed the interaction.
Awesome. All right. Well, thank you very much, guys. Appreciate you joining.
Thanks. Take care.
Thank you.