Okay, so thank you, everybody, and good morning. Appreciate everybody being here at the Citizens JMP Life Sciences Conference. Really excited to be joined now by Aquestive Therapeutics and CEO Dan Barber. So Dan, welcome.
Thank you.
Aquestive is a company that has an oral film technology which has yielded several approved products already. Focus right now is what we view as two exciting candidates in development. The first is an oral epinephrine, which has just read out a pivotal study and is heading towards an FDA submission by the end of the year. And then the second product is an oral diazepam for epilepsy patients, which has been approved for a pediatric population, again, very recently. So Dan, with that, I'll turn it over to you. Say welcome and just ask you to give a brief intro and overview of Aquestive.
Yeah, no, thank you, Jason. Great to be back again this year. As I was thinking about coming this year, I actually looked back two years. Two years ago this week, I had the honor of being named Aquestive CEO. Three things happened in very rapid order after that. One, the day they announced me as CEO, I tested positive for COVID. I think I've told you that. So that was fun. Two, I spent time with Ernie Toth, our CFO, who's here with me today and his team, and realized we only had a few months of money left. Not only that, nobody almost nobody, I should say, wanted to give us money. Three, I had to come here and spend time with you, right? So I looked.
It wasn't all bad. So it wasn't all bad.
So I looked back at my notes. And it's funny now, two years in, I made a lot of promises that day. I promised that we would move away from our CNS commercial team, where we were losing money. I promised that we would create Anaphylm epinephrine sublingual film as our lead asset. And as Jason mentioned, that's indicated for the treatment of severe allergic reactions, including anaphylaxis. I promised that our Libervant diazepam buccal film product that Jason also mentioned that we wouldn't abandon it. We would find a way to bring it to market. And I promised that we would fix our financial situation. We were about to start repaying our debt. We had very little cash. We had a base business that was in flux. We had, I think, six lawsuits at the time. In some cases, we were suing people.
In some cases, the other way around. So, I made a lot of promises right away, saying, yeah, we're going to fix all that, right? So, I'll stop using I there and tell you where we are two years later. We've actually done all of those things. Aquestive, excuse me, Anaphylm last month or two months ago, read out on our phase III study. So, we'll talk about that today. And it is a great place to, we believe, file by the end of this year. Libervant, two weeks ago, got approval from the FDA for a subpopulation. We refinanced our debt. And we have less debt than we had two years ago. We have plenty of cash on our balance sheet, thanks to a really solid group of investors who've believed in us. And we've made our base business a part of the story that is compelling again.
We grew in 2023. We grew in the first quarter on that base business. Sitting here today, it feels great. It feels like we, as a management team, have done all the right things to get to this moment. Now we need to take advantage of the place we're in.
Great. So let's start and congrats, I should say. That's not a full undertaking. Let's start with Anaphylm, oral epinephrine candidate. I know this sounds obvious, but the market is clearly driven by injectables. Can you just talk to us about the data that you have behind the need for alternatives to injectables?
Sure. Yeah, and I'll start with, I guess, a personal story almost first. And you and I always talk about our kids when we have a chance to update. I have two teenagers. But when they were younger, I coached a lot of sports: soccer, baseball, basketball, softball. And inevitably, and it's May, so think of going onto a baseball field or a softball field. At the end of the day, you have 15 or 20 kids, many of whom are congested from seasonal allergies or whatever, showing up for, let's say, baseball practice. And inevitably, every year, there would be a parent who'd walk up, and they'd have their little zipped bag. And they'd say, here's Johnny's EpiPen. I'll be back in two hours. If he needs it, give him the EpiPen.
As a coach, or even as anyone in the community, that's a really hard place to be, right? Because I'm not looking to give an EpiPen to anyone's child. I will if I have to. But I'm sure going to wait until things are really bad, right? Because I don't want to do something I shouldn't do. So if you think about how that would play out during a baseball practice, the child has to start developing serious symptoms. I have to go back to the bench or wherever I put the EpiPen, find it. I have to take it out. I have to figure out how to use it. And then I have to actually give it. And that, when we do our studies over and over again, is the issue with anaphylaxis and where bad outcomes happen. It's time. It's the time of finding the product.
It's the time of administering the product. It's the time of the actual uptake of the epinephrine, which is where, Jason, as you know, spending time with us, we think we're differentiated. Because our product can be carried anywhere, right? I keep it. I actually carry two at all times as placebos just to get the experience: one in my coat. And I also put one on the back of my phone at all times. So we believe, from a time perspective, people will have it with them. The other is the ability to take it orally. So you just take it out of the foil sachet, put it under your tongue. And then the third, which is the really fun science, which I know we'll get into, is the uptake.
How fast, how long does it take from the time you put it in your mouth to actually get a really good concentration? In our case, in our phase III data in March, we had a time to maximum concentration of 12 minutes. Now, 12 minutes is faster than the autoinjectors in that study. It's faster than the manual IM in that study. And it's faster than any of the competitive data that we've seen for the nasal sprays that are in development.
And so you talked a lot about time there and the importance of time. I think the other key piece here is you're talking about the scenario where the child, the parent, actually has the EpiPen. There's clearly a lot of people that should have an EpiPen that don't carry an EpiPen. So can you just walk us through that dynamic there of why people don't even have the rescue medication they need?
Yeah, well, first, in terms of just the prevalence, there are and depending on which estimates you want to use, we use the FARE advocacy group estimates, because they're one of the bigger advocacy groups in the space. They estimate there's around 40 million people in the country who should have a rescue product on them because they have some level of potential need. There's an estimate that around 17 million, so about 5% of the population, will have a severe allergic reaction in their lifetime. And yet, every year, there's only 4 million scripts written for the autoinjectors. So 4 million, 17 million, 40 million, clearly there is a gap between what people are actually carrying and what they should be carrying. When we look at the why, behavior is a big part of it. And that behavior is, how hard is it to carry the product?
Do I want to carry it with me everywhere I go? Will I actually use it? There's an odd behavioral element that we've learned that people don't want to use their autoinjector because that signifies that they're actually sick, which, if you think about it, is kind of a reverse psychology perspective. But we believe, with an oral product, that we can get people to use the product right away as their symptoms start to occur.
Great. So as we said, phase III data read out a couple of months ago. I think one of the most encouraging parts of it is the data were not surprising, right? They looked very consistent with the profile that you've shown for this candidate for a couple of years. And to your point before, one of the most important things is how quickly the drug gets into the bloodstream. So can you just walk us through what you saw in that pivotal phase III trial, what the goal of the trial was? And again, let's not forget what FDA asked you to do in this study.
Sure. Yeah, so it is a, as it's called, a 505(b)(2) program, which epinephrine, you can't do an efficacy study because you're not going to induce anaphylaxis and then see if people are okay. It's simply not a study that can be run. So the FDA has, both with us and the other companies in this space, given pretty clear direction on what needs to be shown. And what you need to show is that you're comparable to the products that are out there from the traditional peak levels, so Cmax and area under the curve or exposure. And what's really exciting from our phase III study is, in the first 30 minutes, we are bio-comparable for both Cmax and AUC. In the first 30 minutes, we are bio-comparable to the autoinjectors. So if you think about anaphylaxis, 30 minutes is a lifetime.
From our perspective, we think that data is very compelling. We also saw in that study a very clean safety profile, which we're happy about, and our pharmacodynamic markers, which the two markers in this space that people track are blood pressure and heart rate. If you ask a physician, what do you want to see? I want to see blood pressure go up. I want to see heart rate go up. We show an impact on blood pressure and heart rate at two minutes. The reason it's at two minutes is because that's the first time we look. So we actually could potentially be even faster than that. So two minutes, PD markers go up. We are bio-comparable for 30 minutes and have a great safety profile.
So another part of the phase three study, when you think about that PK profile, is, like you said, you're the same, if not very, very similar in that first 30 minutes. But then in the second 30 minutes, there's an argument that the trend's off a little bit away from the autoinjectors.
Yes.
FDA asked you to look at repeat doses. So can you just walk us through the repeat dose data and the confidence that you have that you're addressing a problem for beyond 30 minutes?
Sure. No, and I appreciate that question, Jason, because I think there's a real opportunity for the company here. And yes, as all of you know, with every drug development, with every product that's in drug development, there's always a spot where you need to convince the FDA that you're in a reasonable place, right? So for our competitors, that first 10 minutes, they're actually much lower than the autoinjectors. And that's a spot they have some convincing to do, right? We look really good in that spot. But if you go to the backside of the curve, so 45 minutes, 60 minutes, we are actual concentrations, as Jason mentioned, are lower than the autoinjectors at 45 and 60 minutes. In terms of total exposure, we're comparable, but not those actual data sets.
So what we were able to show in the phase III clinical study we just ran is a couple of things. One, we released the actual data sets for 45 minutes and 60 minutes. And you can see that there's actual overlap between our data set and the autoinjectors. So, from a statistical perspective, they are not different. Two, we know that we stay above 100 pg/mL, which is the level in literature that's suggested as the therapeutic effect for or the start of the therapeutic window for epinephrine. And then third, as Jason mentioned, we have a repeat dose arm. So we showed that if you take a repeat dose, and we've done it at 10, 15, and 20 or 25 minutes at this point, that you get a nice effect with a very good tail.
What I think is really compelling about the repeat dose, and I didn't really think about until we had this data, is if you think about someone progressing through the stages of anaphylaxis, they take our product or an EpiPen or whatever, and let's say 15 or 20 minutes in, things have gotten worse. Now it's very serious. Now you're starting to get into a spot that is very severe. With our repeat dose, we saw two things that we think are really compelling. One, our Tmax, so our time to peak, went from 12 minutes with the first dose to 8 minutes with the second dose. So we're faster with the second dose. And two, we are more than proportional in the second dose. So what does that mean?
That means that rather than getting this amount that you got with the first dose sorry, I'll go up here, this amount with the first dose, you're getting more, right? So that severe person who's in a situation where they need a second dose, they're getting faster Tmax, and they're getting more epinephrine. We think that is the right place to be when someone is in a severe state.
You mentioned the competitors. We saw an FDA advisory committee a few months ago, which I think reaffirmed a lot of what you've just described, that the FDA wants to see a PK profile that looks similar to the autoinjectors and intramuscular injection. They want to see fast acting, and they want to see durable. But almost all of the conversation was on PK, not PD.
Right.
So we actually heard some of the physicians commenting at that AdCom, "Come on, why aren't we talking more about blood pressure, heart rate?" Traditionally, when we talk about increased blood pressure and heart rate, we start to get worried.
Yeah.
Where do you think the confidence level should be that the two are mirroring each other, i.e., the blood levels go up, blood pressure and heart rate goes up? And is there a point or any scenario where you'd be worried that blood pressure and heart rate go up?
Sure, yeah. I'll answer your last question first. Obviously, if blood pressure or heart rate go up too much, that could be an issue. So what we also disclosed in our data is the actual range of change, not only the change in blood pressure and heart rate, but the absolute numbers and what we're happy to see. And I don't have our Chief Medical Officer here with me today. But what we were happy to see is we stay within a safe range at all time points, which is great. But yes, there is an interesting dynamic with this product in particular, where the FDA is doing exactly what they have to do, right? The mandate is to use pharmacokinetic measures to show comparability. And so that's where they're going to focus.
And they've even said to us, and I believe, from what we've seen, our competitors, that while pharmacodynamic data is interesting and compelling, it's not going to be used as the primary source for approval, right? It's just not the guidance they're following. When you talk to physicians, so when it gets to the commercialization and the marketing of the product, PK has a place. The speed part of PK, I think, will be important. But PD becomes much more important. And you did hear at the AdCom, "the practicing physicians focus on, hey, tell me whatever you want with pg/mL at whatever time, but tell me if the heart rate went up. Tell me if blood pressure went up." So in a real-world setting, that data will be very important.
Got it, okay. You read out the pivotal study a couple of months ago. You're headed towards a target NDA submission at the end of the year.
Yes.
There's a couple of supportive studies that have to be run at the same time. Can you just walk us through what needs to be done between now and the NDA submission? And I guess, really importantly, how do you think about the risk profile of those different studies now that we have the pivotal data out of the way?
Sure. No, great question. Yes, so there's three supportive studies that we're doing right now. I'll say they're mainly in parallel. The first one is what we call a temperature pH study. So in this one, it's very simple. In our data that we released in the last earnings call on our website, we did actually put the actual designs of these studies for people who want to see it. But the temperature pH study, very simple study, we give people hot liquid, cold liquid, lemon juice, different things to impact the conditions of the oral cavity. We wait a minute, and we give our film. And then we check the differences in absorption. So from a non-clinical perspective, the work we've done in the lab, we don't expect any differences. The amount of liquid you're giving should not impact the temperature or the absorption rate of the sublingual tissue.
So from that perspective, we feel pretty good about what we should see. Having said that, even if we see a change, we don't think that is a material issue to the program. That is just information that can be used to align with the repeat dose need, right? The second study we'll run is even simpler than that study. This is just a self-administration study, which traditionally, the human factors work we're doing should be enough for the FDA. But I believe, given this disease state, not just with us, but with others, they're being extra cautious. So they asked us to run a study where subjects actually administer the film themselves. So it'll be two arms. The clinician administers it. They come back. They wash out. And then they administer it themselves. And we check and see if there's a difference.
Now, just remember, if you look at the film strip, there's actually only three steps. You rip it open. You take the film out. You place it under your tongue. I guess four steps. You lower your tongue. So we do not believe, especially with the number of studies we've run and the number of different clinicians and CROs who we've worked with, we don't expect a difference in that study. The third study is an oral allergen study. So in this case, previously, we thought the FDA would require us to do an angioedema study. So one of the effects of anaphylaxis is edema, swelling, right? You have swelling of your throat, your tongue, your lips, your nasal cavity. Anything that can swell on a mucosal surface may swell.
Now, it doesn't swell like one of the misconceptions that I've heard in the marketplace is that it's like I'll use a bad analogy. It's not like popcorn, where you have a kernel, and then instantly, you have a puffed up, complete edema, right? It is a progression as time goes on. So what we'll be able to study in the oral allergen exposure study is exposing people to an allergen, seeing how the edema progresses, applying our film, and then tracking those results versus a baseline. So again, we believe edema should, if anything, speed up absorption. And we think that study will be a very good telling study for us.
Got it, great. Then just from a manufacturing perspective, obviously, like I said, you've had several products approved by FDA. You've had a manufacturing facility producing, I'm going to say, millions and millions of oral film strips in the past. So just from a CMC perspective, are you all good for the NDA submission now?
Yeah, look, the core of this company, and we're coming up on 20 years. I think we're 19 years old as a company now. The core of this company is still that manufacturing CMC base. In the first quarter, we produced over 40 million doses of product that we shipped out to our partners, who then ship it out to patients. So the CMC part of our business operates every single day and is a core to what we do. We actually already had an end of phase II meeting with the FDA on CMC. And you guys haven't really heard about that program, even though we press-released it or that meeting, because there was nothing of consequence that the FDA found. So from a CMC perspective, we're in great shape.
Right. Last piece, and clearly, in some ways, the most important piece is getting ready to commercialize the product. Can you just talk us through your plans? A, are you thinking about a partner? Can a partner be helpful here? And B, what's the work that needs to be done? We know epinephrine is the standard of care, right? That this is about how do you get people to use it faster, how to get more people to use it. But what are you getting? What are you doing? And when are you starting that commercial readiness work?
Yeah, well, the most macro thing for me is we talk as a team about where do we go is thinking about it not as a black and white choice of you either give it to someone else or you do it yourself, right? Distribution in this space, in any space in the pharma industry, is just incredibly complex and obtuse, might be the way to put it. So from our perspective, we're looking at distribution as a whole picture. Yes, are there people who can help us be further along or deeper into the marketplace? Sure, if they can be helpful, happy to work with them. Yes, there's a spot where we know we can play as a small company and still be very targeted. So the top five deciles in this space are all allergists and pediatricians. That's something that we can handle.
So what we're doing today is putting the practical pieces in place to make sure we're ready for that launch. We've hired the first of our commercial infrastructure. We've brought in an agency of record to have a marketing campaign. We've hired a market access group to help us think through the market access piece of how we put things together. So you'll hear us, over the months to come, really start to talk about that commercial piece. And I do believe that we'll have a lot of progress quarter after quarter.
Great. So we spent, obviously, a lot of time talking about Anaphylm. I don't want to forget Libervant. Congrats again on the recent approval.
Thank you.
Can you just walk us through, A, what you're approved for and the age group you're approved for, what the need there and size of that opportunity is? And then we'll go on into talk about your plans to launch the product.
Sure, yeah. No, and it's interesting, having been around you and I have both been around this story for a long time. And it's interesting having to remind people that Libervant is valuable. Libervant's not only valuable to patients and caregivers, but it's valuable to Aquestive. We have the opportunity, in the two -five-year-old space, to be the only product available besides a rectal gel. So, think about it. Your child, if you're in the unfortunate situation where your young child in that two- to 5-year-old space has been diagnosed with epilepsy, you're on a maintenance medication, and you're told your child may have breakthrough or seizure clusters, and you're told, well, the only product we have for you is a rectal gel. Now, we have a buccal film that can go just inside the cheek. We think that is very compelling.
From a market-size perspective, there's around 55,000 scripts a year right now written in that space. We know that is not full. That's not the full prevalence. So we do think, just like the other age groups, when alternate products launched, all of those alternate age groups doubled. So we think that potential is there for this age group as well. From launching the product, right now, we are actively building distribution and market access. So we're on the path to being able to fully provide people with this product in the coming months. The question for the company, and the one I owe everyone an answer on in the next couple of months, is do we build the sales team ourselves, or do we use someone else's sales team? If we have to build the sales team, it will be 10-ish people.
If we use someone else's capabilities, obviously, we don't need to do that part. So from a decision-making perspective, on our side, the biggest factor we will use is performance. Can the other side perform? While money is important, getting another $10 or $20 million as an upfront from someone just for them to take our product and not perform doesn't seem like a good move.
Got it. You have tentative approval from FDA for the adult population, an older pediatric population as well.
Yes.
You're waiting for an orphan exclusivity period to expire.
Yeah.
But you're also not waiting for an orphan drug exclusivity period to expire. So can you just talk us through why you think the product should be available today and what you're doing to try and get it available today?
Sure, yeah. And look, this is if you go to what caused the company some hardship a few years ago, it really was that determination that the FDA made around the tentative approval, right? So from our perspective, the patient population, six and up, continues to have a need for alternate delivery products and products that can serve the patient population better than what they have today and will continue to work with the FDA to see if we can get into the market ahead of 2027.
Fantastic. Well, Dan, really appreciate you being with us this morning.
Thank you, Jason. Appreciate the time.
Looking to see the progress for the rest of the year.
That's good.
Thanks.