Good day, and welcome to the EPIPHAST II update call. At this time, all participants are in listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. As a reminder, this call may be recorded. I would now like to turn the call over to Dan Barber, CEO of Aquestive Therapeutics. You may begin. Thank you, operator, and good morning, everyone. Thank you for joining the call today. We appreciate your time and continued engagement. Before I begin, you will see that we have included our company cautionary forward-looking statement made under the safe harbor provisions of securities laws on slide two of our presentation. As a reminder, information included in this presentation is based on the company's review and evaluation of the clinical data regarding AQST-109. All conclusions and determinations contained in this presentation are subject to the company's further analysis of the clinical data. The ultimate determination of the safety and efficacy of AQST-109 will be made by the FDA. We ask that you keep these cautionary statements in mind when reviewing this information. Now, on to today's announcement. This morning, we released our EPIPHAST II clinical study results, along with the presentation deck that is available for download on our website. I have asked Ken Truitt, our Chief Medical Officer, and Steve Wargacki, our Vice President of R&D, to join me today. They will be walking you through the results. Once they have completed their presentation, we will open up the line for Q&A. Before I hand over the discussion to Ken and Steve, let me give you a few of my thoughts. In my view, these results represent a significant step forward for Aquestive and for our AQST-109 epinephrine sublingual film program. This is the last piece of clinical data needed prior to our end of phase II meeting with the FDA. First, as far as I'm aware, we remain the only company with an oral epinephrine product in development for the treatment of severe allergic reaction, including anaphylaxis. Over 40 million Americans are at risk of experiencing anaphylaxis. Yet each year, less than 4 million prescriptions are filled for epinephrine auto-injectors. To me, this indicates a significant unmet need continues to exist in the treatment of severe allergic reactions. I believe that an oral product will help increase the number of instances where a rescue product is readily available during the occurrence of a severe allergic reaction. I also believe an oral product will reduce the barrier to usage during the onset of a severe allergic reaction. Second, as Ken will remind all of us, speed of epinephrine absorption into the bloodstream is perhaps the most critical component to stopping a severe allergic reaction. Based on the results we are seeing, our speed of epinephrine absorption compares favorably to the gold standard of treatment, the EpiPen. This can be seen in our median time to maximum concentration of 12 minutes, which is more than 10 minutes faster than the EpiPen data observed in our EPIPHAST II study. Third, the simplest way to understand potential therapeutic effect is to look at changes in blood pressure and heart rate. Here again, after only a single dose, AQST-109 compares favorably to EpiPen, with maximum changes from baseline seen in well under 10 minutes. Even more compelling, Ken and Steve will show you that in the few instances where a second dose is needed, AQST-109 shows even faster absorption into the bloodstream when compared to the initial dose. This is truly remarkable. I believe these results are very compelling, and we are looking forward to sharing this data with the FDA. AQST-109 represents significant scientific innovation in this space. With patents that will extend to 2040 and beyond, we plan on providing this product to patients for years to come, if approved by the FDA. With that, I will turn over the call to Ken. Thank you, Dan. I'm excited to be here and speak today. I look forward to interacting with you over the months to come and to provide clinical and medical leadership to the team here at Aquestive. Before we get into the detailed presentation, I'd like to highlight a few key takeaways, which are noted on slide 3 of the presentation. By benchmarking AQST-109, a sublingually administered oral film against EpiPen 0.3 milligrams and 0.3 milligrams of epinephrine delivered as a standard intramuscular or IM injection. Importantly, the latter is the reference listed drug, or RLD, serving as a comparative standard for discussions with the FDA. In terms of results we'll present today, first and foremost, we confirm a shorter time to peak plasma epinephrine level, or Tmax for AQST-109 versus either the EpiPen or 0.3 milligrams of IM epinephrine. Respective median values were 12, 22, and 45 minutes. In an ensuing slide, I'll discuss why seconds and minutes are important in treating allergic reactions. Next, while repeat epinephrine doses are infrequently needed, our data show a second administration of AQST-109 can rapidly boost plasma levels and bolster the magnitude of response to one that could occasionally be needed to stabilize anaphylaxis in the field. A repeat dose of AQST-109 delivered peak plasma levels after just eight minutes, comparing favorably with the repeat dose profile of the reference standard product delivered in the same time period. The ability to quickly deliver an effective second administration when and if needed is an extremely positive attribute, particularly in a life-threatening condition. Finally, our data continue to show a safety and tolerability profile reflective of the known physiologic effects of acutely delivered epinephrine and in line with those of both EpiPen and epinephrine delivered by standard IM injection. We saw no serious or severe adverse experiences and no untoward outcomes or sequelae of notable concern. It is always reassuring, and keep in mind the assessment of potential risks and benefits is in the context of a potentially fatal condition. To start, it's important to remind everyone of the serious nature of this disease state and the need for fast intervention. Slide four shows potential symptoms and organ system involvement in anaphylaxis. Anaphylaxis, or more precisely, anaphylactic shock, is the most feared outcome of an allergic reaction. Sometimes progressing rapidly to involve multiple organ systems and increasing in the severity of symptoms. Untreated, it can lead to hospitalization, a need for extended critical care, and ultimately to death from respiratory failure and hemodynamic collapse. Initially, patients may experience urticaria or hives, as well as mild swelling in the periphery, all classic for a histamine-mediated response. In the setting of food allergy, early symptoms can reflect gastrointestinal cramping, nausea, and vomiting. However, when involvement spreads to include swelling of the oral cavity, lips and tongue, and airway obstruction accompanied by bronchoconstriction, the situation becomes life-threatening. When vascular dilation leads to a dangerous drop in blood pressure, heart tries to compensate, but ultimately delivery of oxygen to the brain and other vital organs is compromised. Anaphylaxis is a medical emergency, and the only effective acute intervention is with epinephrine. Slide five reinforces its speed where time to treatment is important. Epinephrine can stop an avalanche leading to disaster, but must be administered early during a window of opportunity. Minutes and seconds are important as timely delivery opens airways and shores up the cardiovascular system, including leaky capillaries responsible for early swelling and angioedema. Epinephrine also has inhibitory effect on mast cells, direct effectors of an allergic response and responsible for histamine release. Unfortunately, as each second goes by and anaphylaxis progresses, the magnitude and extent become more difficult to reverse. Although administration in the field can still buy life-saving time, stabilizing the patient until more sophisticated medical care is available is what then becomes most important. Key is how fast epinephrine gets into the bloodstream and to affected organs and tissues. Only then can epinephrine exert palliative effects throughout the body. While allergic individuals are encouraged to carry around epinephrine syringes for direct injection, the reality is that the majority of patients do not carry their auto-injector. A clear unmet need exists for a new administration method that enables both fast delivery to the bloodstream and is truly portable. With that, I will turn it over to Steve to walk you through our trial results. Thank you, Ken. I'll start by just briefly summarizing the study design on slide six of our presentation. EPIPHAST II was a five-arm study conducted in healthy adult volunteers. The first three arms compared AQST-109 to both the 0.3 IM injection as well as to the EpiPen. The other two arms compared a repeat dose of AQST-109 to a repeat dose of the 0.3 IM. For both products, the repeat dose was administered 10 minutes after first dose administration. During the study, we monitored for pharmacokinetics, pharmacodynamics, as well as safety and tolerability. Flipping now to slide seven. From the top-line data we received, we are excited to share that AQST-109 continues to perform as it has throughout our development program. Ken just discussed the importance of getting epinephrine on board as fast as possible during an anaphylactic reaction. You can see, based upon the box and whisker plots on the left, that the Cmax produced by AQST-109 within 15 minutes of dosing is higher than that of the 0.3 injection and comparable to that of the EpiPen. The levels produced by AQST-109 are well bracketed by both injectable products, suggesting efficacy on the low end and safety on the high end. The profiles on the right show that with the exception of the five-minute time point, the profiles for AQST-109 and the EpiPen are virtually indiscernible. Also, in this profile, you can see the impact of repeat dosing of both AQST-109 and the 0.3 IM. While the repeat administration of the IM dose has virtually no impact on the PK profile over the first 20 minutes after the second dose administration, AQST-109 is rapidly absorbed, providing additional epinephrine within two minutes of second dose administration. In fact, as we'll talk about later, the second dose provided peak plasma levels just 8 minutes later. Moving on to slide 8. Tmax values obtained after single administrations show AQST-109 providing the fastest median Tmax at 12 minutes compared to 22-minute Tmax for the EpiPen and a 45-minute Tmax for the 0.3 IM. The 12-minute Tmax for AQST-109 has now been confirmed across multiple studies and a variety of administration conditions. With the Tmax of EpiPen nearly double that of AQST-109, it truly shows just how quickly patients may get relief from this life-threatening reaction. We now turn our attention to slide 9, which references the pharmacodynamics, specifically the systolic blood pressure and heart rate. Both are expected to go up in response to epinephrine exposure, and both are used as surrogates for the therapeutic effects of epinephrine to the cardiovascular system as well as the respiratory system through adrenergic receptor activation. The speed of AQST-109 is evident here as the systolic blood pressure rapidly increases after administration. You can see the EpiPen having a similar response for both measures, while the more slowly absorbing IM dose has a lag in both responses. Interestingly, the EpiPen did not produce a greater PD response despite a higher overall Cmax compared to AQST-109. This suggests, at least hemodynamically, there is no measurable benefit to having a higher Cmax. On slide 10, we discuss another important outcome of the EPIPHAST II study, which is the confirmation of the ability to deliver a second dose. With IM injections, local vasoconstriction in the tissue requires a second dose to be administered in a new location to ensure an adequate effect. Given sublingual administration would be repeat dose at the same location, it's critical to ensure that the second dose can be administered and absorbed effectively. EPIPHAST II showed unequivocally that for every subject in the study, second dose is rapidly and effectively absorbed. In fact, the second dose reached Tmax 8 minutes after second dose administration. That's faster than the single administration and faster still than a single administration of an EpiPen. Now, turning to slide eleven. EPIPHAST II was a controlled study in healthy volunteers. This means that a second dose was administered to every subject, irrespective of what their plasma epinephrine levels and the magnitude of the mechanism-based pharmacodynamics were after the initial dose was given. This resulted in some very high plasma epinephrine levels. However, as noted by key experts in the field as well as the published literature, the need and use for a second dose is quite rare. When a second dose is required, additional epinephrine is the standard of care. As demonstrated in this study, irrespective of what your levels were at the time of second dosing, additional epinephrine was delivered. One reasonable perspective is that the need for the second dose is tied to those who may have lower drug levels at the time of second dosing. Within this context, a post-hoc analysis was performed. We took individuals who were at epinephrine levels below 300 picograms per milliliter, a very conservative number, and analyzed these subjects specifically. What we found for this subset is that every one of these subjects responded to the second dose with increased plasma levels, but that those levels were within the observed values of the repeat dose IM. Because AQST-109 has such a rapid Tmax, someone dosing a second time at, say, 15 minutes would likely be past Cmax. If their symptoms persisted, additional epinephrine is warranted. With the IM, patients are still 30 minutes away from their Tmax. While a second dose is the right choice for someone at that time to control their symptoms, they still have a large and potentially unnecessary amount of epinephrine still to come. In this sense, AQST-109 may provide doctors and patients an alternative that avoids unnecessary exposure after symptoms have subsided. The final but equally important piece we'd like to cover today, as noted on slide 12, is the safety readout from EPIPHAST II. AQST-109 continued to be safe and well tolerated, consistent with all studies to date. In comparison to the EpiPen, you'll see that EpiPen had a much higher rate of palpitations, 4x-5x that of AQST-109. This is consistent with what is known about epinephrine, which is above a certain level, adverse events are increased, but not necessarily effectiveness. Lastly, despite some of the very high exposure levels seen with the repeat dose of AQST-109, the rate of palpitations was only slightly higher than that of a single dose of EpiPen. In summary, concluding on slide 13, we are very pleased with the outcome of the EPIPHAST II trial. We continue to confirm the Cmax of AQST-109, which as shown in the data today, had a faster Tmax than the EpiPen. We showed that our levels fall right between the 0.3 IM and the EpiPen, bracketing safety and efficacy from the high and low sides respectively. We also successfully demonstrated the ability to deliver a second dose of AQST-109, and that second dose is even faster than the first dose. Lastly, both single and repeat administrations are safe and well tolerated. With this data in hand, we are eagerly awaiting our end of phase II meeting with the agency in Q4 of this year. I'd like to thank you all for listening, and we are happy to answer any questions. As a reminder, to ask a question, please press star one one. Our first question comes from Gary Nachman with BMO. Your line is open. Hi. Good morning. This is Denis Reznik on for Gary Nachman. Congrats on the solid data. Could you just provide any insight as to what you think the next pivotal PK study will look like? I've got a follow-up after that. Sure. Good morning, and thanks for the question. I'll hand it over to Ken Truitt in a second, who will walk you through the next study design. In terms of the next steps, just to make sure we set the base right, we'll be going to the FDA in Q4. We'll show them the design of the study that we're planning, and then we'll begin the study as quickly as we can after that meeting with the FDA. With that, Ken, could you walk through your thoughts on the study design? Yeah, sure. The next study will be a replicate dose comparative, PK and safety study, where we benchmark AQST-109 against our reference-listed drug, so 0.3 milligrams, epinephrine delivered by standard IM injection. Okay, great. Just a quick follow-up. Just following this data, could you talk about how you view the asset long term from a partnership point of view? Thank you so much. Yeah. Well, from a partnership standpoint, let me be clear on our strategy and how we view the steps going forward at this point. We see AQST-109 as a product that has a large unmet need and has a large potential in the marketplace. We're focused on bringing it to the market ourselves. We will be, over the next few quarters, talking about more about what the sales profile would have to look like and the call points. At this point, we're not looking to partner this product out to someone else. This is the product we will be bringing forward. Okay, great. Thank you so much. Our next question comes from Jason Butler with JMP Securities. Your line is open. Hi. Thanks for taking the questions and congrats on the results. First one, sorry if I missed it, but can you, if I didn't, can you talk about how AUC compared between 109 and the EpiPen? And then, thinking about the FDA again, how do you think about the focus on Cmax obviously, but also to what extent do you think, excuse me, that Cmax and AUC will be relevant? And also along those same lines, to what extent do you think FDA is focused on the point estimate here versus the 95% confidence interval? Thanks. Yeah. Well, I'll turn it over to Steve in a second. Jason, just globally, we think and hopefully in our comments in the way we presented this morning, we think speed is very important. That's why we think Cmax is an area of focus, not just for us but for the FDA. AUC as Steve will walk you through, is more about the early time points. Before I steal all of his thunder, let me pass it over to Steve. Thank you, Dan. Yeah, you raised good points, and we continue to look at all of the parameters of our pharmacokinetic profile. As we discussed, speed is critical, and we compare very favorably with all of our partial AUCs. The early time points, the exposure you get early, which is critical for creating that bridge as you seek to abate the anaphylactic reaction and receive definitive care. That's both for our AUC and our Cmax values where we're very favorable across the board. Overall, the Cmaxes line up quite well and our total AUC again is within the range of the intramuscular injection. We look forward to aligning with the agency on all those critical parameters. Great. Just one more on the safety and tolerability. Can you just explain to us what cardiac disorders comprises, and how that compares to the palpitation findings? Thanks. Sure. Ken, can you take that one? Yeah. You're asking about the palpitations and what those are and how those are recorded. Is that correct? I guess I was asking more what the cardiac disorders are. You know, obviously. Oh. in cardiac disorders or what else is in cardiac disorders? Any adverse experience term that maps the cardiovascular system would fall under that broader category of cardiovascular disorders. Jason, the key point from our data that we saw is that an EpiPen with a single dose has a higher incidence from a safety perspective compared to our single dose or the manual injection, which we think provides a profile that we're very happy with from our product perspective. Got it. Thanks for taking the questions and congrats again. Thanks, Jason. Our next question comes from Francois Brisebois with Oppenheimer. Your line is open. Hi. Thanks for taking the question. Congrats on the data. Just quickly here, I think it's a little bit based off the prior question, but in terms of the EpiPen time to maybe that relevant hemodynamic threshold, do you disclose that, or is that something that we don't have in this data readout? Yeah. Well, I'll pass it over to Steve in a minute. What Steve and Ken are always good about educating me on is that somewhere around 100 picograms per milliliter is where people would start to talk about therapeutic effect or a therapeutic window. We did not disclose that data in this particular presentation. What I can say is we're very fast and we are comparable to the EpiPen. I think I don't know the numbers. Perhaps Steve does off the top of his head, but we're talking about single minutes. Yes. Yes. Thank you. Yeah, we are. Yeah, you can see that in the pharmacodynamic slides that we presented that both products induce that hemodynamic effect on average within the first measured time point, which is two minutes. You're seeing that increase. We haven't presented the precise numbers on reaching 100 picograms, but they are highly comparable. Okay, great. In terms of the you just talked about maybe how important the systolic blood pressure and the heart rate data is. It seems like there's a little bit of an inversion in terms of the blood pressure and the heart rate between EpiPen and AQST-109. I'm just wondering, is it comparable to 5 and 8 minutes here or is it, does that actually have a real impact? Sure. Well, maybe globally speaking, Ken can just walk you through why systolic blood pressure and heart rate are so important. My memory is I think the difference, I think it was the IM manual injection that actually was inversed. I think the EpiPen was very similar to ours. Ken, if you could walk through that. Yeah. We view it as a very positive finding to see these pharmacodynamic effects early on. In fact, the sort of early inversion on systolic pressure that one sees with the standard IM injection could be in some ways viewed as a negative. Again, as Steve mentioned, we look at the pharmacodynamic measures as a proxy for therapeutic benefit. The inversion could imply a delayed time to therapeutic effect with the IM. Both EpiPen and AQST we would see that as a very favorable result. Okay. Then just lastly on the Cmax here, the single dose epi at a Cmax that was almost double. I was just wondering, is there actually maybe a positive to this as well in terms of the potential AEs? Yeah. You're hitting a very good point, Frank, that we wanna make sure we're clear on today. That is one, to your point, the AE profile for the single dose of EpiPen was different in a less than positive way compared to ours. Two, as I'll hand it over to Ken in a second. We don't see from a pharmacodynamic perspective any benefit given to the patient or the subjects in the study for that extra Cmax level that we saw on the EpiPen. Ken, I'll let you Yeah, I think Steve hit on that pretty nicely in that, the additional Cmax doesn't come with any additional pharmacodynamic proxy or there's no additional bang for your buck, so to speak. It's additional exposure, but without correlation with what we would see as a proxy for efficacy. Perfect. All right. That's it for me. Thanks for the question. Our next question comes from Thomas Flaten with Lake Street. Your line is open. Hey. Thanks for taking the questions. I hope I'm not mangling the science too much, but I think one of the reasons you guys went with a prodrug was because of the rapid onset of the vasoconstrictive qualities of epinephrine. Were you surprised by how powerful the second or the repeat dosing was in terms of Cmax? Or am I misunderstanding the MOA there? Sure. Yeah. Thomas, I'm gonna pass that over to Steve to walk you through that. Sure. Thanks. Thank you, Tom. The prodrug allows us to absorb very, very quickly through the submucosal space and get that conversion. We're not surprised that the second dose absorbs very quickly as well. You know, keep in mind that we did not do a repeat dose of the EpiPen in that study. Given the performance of the EpiPen with the single administration, you'd expect to see similar levels from that. Should it have been repeated? However, with the IM, you know, that slow uptake that they can clearly see in the pharmacokinetic profile, you know, is that elongated impact for the effects of that second dosing, and that's not what you need during a, you know, a rescue situation where what you wanna see is that rapid absorption. And then- Surprise is probably. Go ahead. Sorry, go ahead. No, please. I was gonna say surprised is probably the wrong word. Really happy to see it is probably the right way to put it. Fair enough. Then on slide seven, you guys called out the 5-minute mark where there was a pronounced difference in the way those curves look. Can you talk a little bit about the relevance of the AUC difference that's caused by that rapid upswing by minute 5 on that right-hand panel? Steve, you can take it. Yeah. Yeah, happy to. Yeah, there is a difference. You know, you can clearly see there's a difference in that profile at the five-minute mark on average. But the difference in that AUC, you know, isn't as we've highlighted with respect to the pharmacodynamic effects and everything that we just spoke to previously. There's no real benefit there, and we pick up by the next time point. Again, a very strong comparison in those profiles. Excellent. Best bet on initiation of the pivotal. Do you think it's gonna be early next year? Thomas, what I would point to is, and I think a really important message out of today is we remain on track. We said we would have this data in Q3. Here's the data in Q3. We said we would meet with the FDA in Q4. We have our meeting lined up for Q4. We continue to track to our goal of filing before the end of 2023. Whether the pivotal study starts in December, January or February does not impact the filing time at the end of the year. None of those time points are critical tasks. Having said that, I think you will see us start the pivotal study as quickly as possible after the FDA meeting. Got it. Appreciate it. Thanks, guys. Again, to ask a question, please press star one one. Our next question comes from Andreas Argyrides with Wedbush. Your line is open. Hey. Yeah, good morning. Thanks for taking our question. Just a quick one on the use of EpiPen. What was the rationale for not allowing a second dose and thinking about using it as a comparator in future trials? Thank you. Sure. Morning, Andreas. Thanks for the question. The repeat dose work was part of that. In past calls, we've talked a lot about the need to do characterization work, right? We wanted to go into the FDA in our end of phase II meeting with a very robust package, and we have focused on what is necessary for our filing. It is simply just not necessary to have the EpiPen repeat dose data for our filing. If we were to do it would simply be for informational purposes. As Steve pointed out, we would fully expect it to look very similar to what we saw with our second dose. In terms of the comparator, Ken and Steve, when they have their meeting with the FDA, will continue to be pointing to the manual IM injection as our reference-listed drug. I think that makes the most sense from just a product development perspective. I don't think you'll see us use the EpiPen as the reference product in our packaging. You most likely will not see that as a comparator in the pivotal study. Okay, great. Thanks, and congrats on the data. Thanks, Andreas. There are no further questions at this time. I'd like to turn the call back over to Dan Barber for any closing remarks. Thank you, Michelle. As you heard today, we remain excited about the results of and the prospects for our AQST-109 program. There's a large unmet need among patients at risk for severe allergic reactions. AQST-109 is the only oral product under development and may help fill that unmet need. We remain on track to meet with the FDA in Q4 and expect to perform our pivotal studies in 2023. With that, thank you for attending the call today, and we look forward to interacting with you again in the near future. This concludes the program. You may now disconnect. Everyone, have a great day.