Okay, let's get started. Good morning and welcome again to day three of the Piper Sandler Healthcare Conference. This is David Amsellem from the Piper Biopharma team. We're delighted to have Aquestive Therapeutics. This is an exciting time for the company, so we have Dan Barber, CEO, and the team up on stage, so lots to talk about. There's obviously the PDUFA coming up, there's commercialization of Anaphylm, and more things to come, but as a starting point, longer term, how do you balance the top priority of commercializing Anaphylm successfully with other clinical and commercial programs? There's Libervant, there's your topical epinephrine prodrug platform, so how do you balance all those different things? And obviously your top priority is Anaphylm, but you do have other things that are, I would say, flying under the radar, so how do you think about that?
Sure. No, and first, David, thank you for having us today. We appreciate it as always. And as you mentioned, I have Sherry Korczynski, our Chief Commercial Officer, Gary Slatko, our Chief Medical Officer, and Ernie Toth, our Chief Financial Officer with me. So you've got the core team here today. And I appreciate you always asking about the totality of our business. Anaphylm is an incredibly exciting product that we are thrilled to be very close to our PDUFA date and bring to market. But it's part of a broader ecosystem that is Aquestive, right? And what people sometimes don't realize is that Anaphylm comes out of a prodrug epinephrine platform that we have great intellectual property around.
We do firmly believe if you look at it as a three to five to seven-year long-term strategy company that half of our value will be coming from pipeline opportunities that are yet to come. Now, your question though is really about balance, right? And clearly in 2026, launching Anaphylm and all the great work that Sherry and Gary will be doing is going to be center stage. Where it lines up nicely for us is our pipeline is early stage enough that the work that's going to be done will not be overly burdensome from a financial position. So we can get through 2026, do the work we need to do on our pipeline to make it meaningful while supporting, using most of our resources to support Anaphylm.
Okay. So you have the PDUFA coming up for Anaphylm soon. I wanted to dive into commercial readiness. So obviously that's important and you're well down that path here. Remind us how you're thinking about the sales force headcount, headcount for other personnel like MSLs, and also how many prescribers you intend to call on initially.
So before I hand it over to Sherry, I do want to just point out to everyone, this has been a two-year journey. So Sherry's been with us just about two years. We're very fortunate. I know she hates when I do this, but we're very fortunate to have her leading the effort with her background from EpiPen and that brand. But we've been building steadily and making sure, especially on the MSL side, that we're out there, we're building awareness. Our MSLs are at all the conferences. We have posters, presentations, all the things you'd expect. But I'll let Sherry give you the details.
Sure. As Dan mentioned, we've been building all along. And so we are on track from a commercial readiness perspective to launch as we've stated publicly later in Q1. From a sales force perspective, if we kind of take a step back and say, well, what is ultimately going to drive the business for Anaphylm? It is the specialists. And so the allergists are the, one would argue, the most important customer here for our sales force and to get that lift that will be required. And we know this market is an inch deep and as I say, 10,000 miles wide. You have your allergists that rate around 30%-35% of the prescriptions, followed by pediatricians. And then you've got a whole lot of stuff, right? PCPs and OB/GYNs, ENTs writing one or two refills annually. So our approach is quite different than our competitors.
We are going to be very, very focused on that allergy segment. We believe that as the specialists write, the others will follow. The pediatricians and PCPs will follow, and so we'll be covering approximately 5,000 allergists, which is the vast majority of allergists in the United States, and we'll be able to do that with between 50 and 60 sales representatives who will be hired post-PDUFA.
Okay. How are you thinking about pricing relative to the EpiPen generics and also neffy? Probably can't answer the question, but I got to ask it anyway.
Look, I suppose one of the benefits of being second is you get to watch the price dynamics play out and understand how it's worked for the people ahead of you. The other nice thing as you just pointed out is you don't have to set your price until approval. What I would say and when we think about our pricing strategy, this does appear to be a fairly stable space. We think we bring a lot of innovation with our product. So we don't think price is what we lead with. We think our innovation is what we lead with. So I think as you see us come to market, we'll be very thoughtful. We're likely to be, as I've said to some people, kind of boring, but we think that we'll be within the bucket of what is known in the space right now.
Yeah. And have you interfaced with payers as of yet? And if so, just talk to your dialog with payers. They're thinking on access, particularly given the early commercial experience with neffy.
Sure. It's a good question, and obviously the benefit of being second is to take key learnings from what ARS has done, and so when we think about the payers, we've been engaging with payers using the pre-approval information exchange. We're talking. Gary was on with several payers yesterday again, and so we believe it's going to be tough like it is for every new product, but we feel strongly that we're in good dialogue with the payers. They see value in the product, and ultimately, we will be entering negotiations post-PDUFA.
Got it. What kind of learnings are you using from the rollout of neffy that could inform both your promotional strategy and also your payer strategy?
Yeah, I think it's a good question, and there are quite a few learnings that we've had, good and opportunities. I think that we're really leaning into our experience in the epinephrine market over the last 15 years. I have several colleagues on my team that were with me 15 years ago when we grew the brand to about $1 billion. And so we're taking those learnings. We're taking the learnings that ARS has had. I think just on the surface, and they've stated publicly, the payers, it's a tough go, right? It takes time, and so we're prepared for that. I think also from a commercialization standpoint, as I mentioned, we'll be focused on the allergists. Our strategy is a very targeted, focused, methodical approach with the allergists.
And so we're going out again, focused with those reps, and we will expand as market access improves, as payer coverage improves, and as sales come on board. We will look to expand accordingly.
One thing to just add on to that. One thing that we've tried to remember is we focus on the patient and the allergist and how we come to market. 95% of the scripts are still auto-injector, right? So the awareness element, the getting people to understand there's new technology besides auto-injector and fighting the behavior of patients in this space where they don't do what they need to do to protect themselves, that is a lot of where we'll focus. And I think there's alignment on any new product coming into the space, but those are things that need to change as time goes on.
Yeah. What will be your approach to DTC both early in the rollout and longer term?
Sure. Again, I'll keep coming back to that focused methodical approach. We have DTC non-personal promotion plans in regards to print, journals, digital, and then over time, again, as market access improves, as really you want the HCPs to know about the product before you heavily engage the consumers, and over time, you'll see our DTC will increase.
Yeah. I wanted to get your thoughts on the extent to which non-injectable modalities can expand the overall market. I mean, and your competitor has been clear that they believe there is some expansion in the market that's happening. And certainly don't doubt it. I mean, the EpiPen has always been underpenetrated. And it has its limitations. But I wanted to get your thoughts on market expansion with needle-free modalities coming in.
Yeah, it's a good question, and I'll go back again 10, 15 years. What we know is this market is huge. There is upwards of 32 - 40 million people at risk for a severe allergic reaction. However, annually, there's only about four and a half to five million prescriptions, and so there is a big opportunity, and as Dan mentioned, one of the biggest challenges is just apathy. And so as folks, they don't carry because of the bulkiness. They don't use because of a needle, and ultimately, by having new options that, as our product will be so easy to carry on the back of the phone, have something that is not injectable, we believe that it will expand the market, and by having, there hasn't been a lot of voice out there in the market for at least a decade.
And so with having two companies now talking about severe allergic reactions and options, we do believe there will be market growth. Market growth, however, I can tell you we grew EpiPen from about 1.5 million scripts, and we tripled that to about 3 million over a period of a number of years. But it takes time. It takes investment. And it's just driving awareness of the risk. But again, I agree. There is an opportunity. How big that opportunity, I think, is yet to be seen.
Sure. So financial question. How should we think about initial launch spend? And how should we think about longer-term spend on Anaphylm commercial support?
I'll let Ernie take that one. He loves it.
Let's put it in the context of we did two very important capital transactions this year of a revenue interest financing with RTW and an equity raise that brought in new investors to the company. And we've publicly stated that we now have the runway to support a launch through 2027. And that includes all the work that Sherry has done this year for pre-commercial activities and also spending next year and the following year of building the sales force and hopefully ramping up. So I think we've publicly said that we would expect to have 50 - 60 reps initially. And that's spend into next year. We haven't given any specific guidance on spend, but I think put it in the context that we're confident with the cash that we now have upon approval that we'll have a credible, hopefully successful launch next year and well into 2027.
David, I do want to just add, Ernie and his team have done a great job of setting this company up to have the financial wherewithal to do a great launch with Sherry. The work he did this year and the work that's ongoing to refinance our debt, which is the last piece of it, has just been fantastic and has been a real change for this company from years past.
Let's move to the regulatory process. Looking a little backwards, you were notified earlier this year you would not need an AdCom. I wanted to better understand how the safety update to the NDA played into the agency's decision here and just talk generally about your dialogue with the FDA from the safety update to being notified about the absence of the need for an AdCom. I think that context will be helpful.
Sure. And I'll start. And then Gary, if you have some comments you want to add, feel free. So AdComs are tricky right now with the FDA, right? How much is they love us versus how much is the bar is just moving around with what's going on at the FDA? And I don't think anybody knows, right? So what we can rely on is our past experience. We have six approvals in the past. We've been through the process multiple times. And quite frankly, we've been through the process where things went well and where things didn't go so well. So we have seen the other side of it. And when I look at how this interaction with the FDA has progressed, it's progressed much closer and along the lines of what our positive outcomes have looked like. And that feels good to us.
So we definitely believe the timing of when the AdCom news was communicated to us aligns with where you would expect them to sit, talk about it, and say, "Do we need one or not?" So that feels good. In terms of the alignment on the safety data, Gary, I don't know if you have anything to add on that front.
No, I would just say that obviously we submitted a 120-day update, as you mentioned, and that went without a hitch. We've had information requests from the agency. Nothing particularly unexpected coming from those requests, and we've put together very thorough responses on all of their questions, CMC or safety or otherwise, and I think it's encouraging that once we did the work and submitted those responses, the agency didn't come back with second-order questions about how we responded. Generally, that's a pretty constructive indicator that they're satisfied.
Are you in labeling discussions?
Look, everyone wants to know that, right? So we right now are entering the zone of when we would expect labeling discussions. We haven't made a decision on how we'll communicate to the public or what we'll communicate to the public. But obviously, between now and January 31st, there's going to be a lot of back and forth, and we'll see how it goes.
Okay. Can you talk to CMC/facility inspections?
Yeah. As you know, David, you've known us a long time. That is a core strength for the company.
Yes, it is.
We were very pleased a couple of months ago to see the FDA audit our clinical research facilities. So that was great. We publicly put that out. We've had recent FDA audits at our site, so we feel good about that, and when we look at the CMC questions and work that we've done, we are very confident in our position and in the dialogue we've had with the FDA.
Let's talk about the body of data surrounding Anaphylm. And I wanted to ask about Cmax, both with and without allergen exposure. It's higher than what is seen for the manual IM injection. Emphasis is on manual IM injection. I get a lot of questions on it. So I think it's important to talk about it. How should we conceptualize this in terms of clinical implications, if any?
Right. So one of the studies that we did was an oral allergy challenge study where we challenged people first to see if they had an oral reaction to an allergen. And the purpose of that study was to the FDA was asking about whether the presence of oral edema, which can occur with anaphylaxis, might actually impact the absorption of Anaphylm. So we were encouraged to find that in contrast to that, that the absorption of the Cmax with Anaphylm was higher with the presence of oral edema induced by oral allergen challenge than it was in the absence of the oral allergen challenge. And both of them were higher than the control group, which was in the gold standard, if you will, in that setting, in that clinical setting, is an IM injection.
We think that that's an encouraging finding that correlates to the product being an effective alternative to IM epinephrine in that setting. It's also notable that we tracked symptom resolution in that same study. We observed a rapid resolution of oral allergy symptoms with the administration of Anaphylm following oral allergen challenge. It correlated with the increase in blood concentration that was measured over time.
Okay. So looking at pharmacodynamic data, so we've seen a greater increase in SBP and DBP for Anaphylm versus the manual IM injection, also a greater increase in pulse. Again, similar question, just talk to any clinical implications here. I mean, how should we think about it from just a safety perspective?
Sure. So remember, our program was done in normal volunteers. The product will be used in people who are potentially suffering an anaphylactic reaction. One of the biggest concerns in anaphylaxis is low blood pressure. And so one of the reasons that epinephrine is the drug of choice is because it reverses and mitigates the declines in blood pressure, systolic and diastolic, that if left unchecked, can lead to significant morbidity and even mortality. So in that context, increases in blood pressure are a desirable effect, a targeted effect, if you will, of the treatment. The earlier and more robust that increase in blood pressure and heart rate are, the better from the perspective of effectively managing anaphylaxis and potentially being able to do so with a single dose without the need for a second dose or the need for a trip to the emergency room.
We're actually encouraged by the profile of Anaphylm in that it provides a rapid, robust blood pressure and heart rate response that reverses relatively quickly and therefore leads to no long-term blood pressure or cardiovascular issues.
Yeah. So I wanted to touch on another topic, which is the extent to which oral swelling, say, swelling of the tongue in the event of a severe allergic reaction, anaphylactic reaction, could get in the way of effective administration of Anaphylm. And this sort of ties into a question I have about sublingual mucosal thickness. I mean, this is not administered on the tongue. It's a sublingual administration. But when you think about competition and chatter out there, oral swelling comes up. So I wanted to help better understand how you're thinking about this.
One of the purposes of the oral allergen challenge study was to look at whether there was an impact of swelling on absorption. In the study that we conducted, about 25% of the patients had some sort of swelling in the oral cavity, tongue, cheek, other areas. So we did look at that. And I mentioned that there was not an observed impact of that swelling on pharmacokinetics or pharmacodynamics. In terms of the sublingual space, the reason that it's an ideal environment for application of this medication, the sublingual mucosa is particularly thin. It's highly vascular. If anybody's looked under their own tongue, they can see the floor of their mouth and what it looks like. It's really an ideal location to place the film. The film adheres rapidly in that location. It begins to hydrolyze and turn into a gel.
It's very difficult to move at that point from the location of administration. We did actually look at various conditions in the oral cavity under which, in terms of blood pressure, I'm sorry, in terms of temperature, pH, presence of sticky substances, presence of liquid, none of them had a detrimental impact on the absorption that we observed in the absence of those various conditions. So we think that it's really an ideal location. And in the event that someone has difficulty with administration for whatever reason, that's one of the reasons that they're provided a second dose, that they get another insurance dose in the event of difficulty.
And David, just to add quickly to that, one of the things I thought was interesting when Gary and team showed our data from that study to our key opinion leaders, one of them just almost automatically offhand said, "Huh, kind of makes sense. When you apply epinephrine film to a spot that has edema, the edema goes away really fast." So I don't see how that's a bad thing.
Yeah. Great. Yeah. Well, there have been others that kind of tweaked it into a bad thing. Yeah. Exactly. Wanted to ask, and I know we had a minute left, so I wanted to talk more about resolution of clinical symptoms. So in the oral allergen study, a challenge study, you cited median symptom resolution of about five minutes, I believe. So help contextualize that relative to currently available modalities.
This is a fairly innovative approach to looking at symptom resolution. It's not something that's been commonly done in the past. I think what we can best say is that it's very rapid. We can compare it to the literature of how long it takes symptoms to resolve after an oral allergy challenge. The literature is in the one-hour range for complete symptom resolution. A 15-minute median resolution time is fast. We also did look retrospectively during our screening for this study. We screened patients for whether they would have a reaction with an oral allergen. We measured retrospectively (this is an ad hoc analysis that we did) how long it took them to. We didn't give them Anaphylm during screening. We looked at how long did it take their symptoms to go away by patient recall. It was over an hour.
So you're looking at a relatively rapid resolution, in part probably because of what Dan mentioned, the local presence of administration in the area that's being affected, but also by the robust pharmacokinetic and dynamic responses.
Okay. Well, I'll leave it there. I wish we had more time, but more to come. Thanks, Ernie. Thanks, Gary. Thanks, Sherry. Thanks, Dan. Thanks to everyone in the audience.