Aquestive Therapeutics Inc. (AQST) Successfully Demonstrates Repeatable and Predictable Oral Sublingual Film Administration of Epinephrine

Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical company focused on developing and commercializing differentiated products that address patients’ unmet needs and solve therapeutic problems, will provide later this morning an in-depth overview of its systemic epinephrine drug delivery program combining its novel prodrug technology and its PharmFilm® technology. At the R&D event, the management team and KOLs will share an extensive review of the science, clinical results, and development strategy associated with two prodrug candidates in development for the treatment of allergic reactions including anaphylaxis. Aquestive has submitted multiple U.S. and foreign patent applications that cover the technology and formulations for its two prodrug candidates, AQST-108 and AQST-109. If granted, Aquestive anticipates patent protection for both drug candidates through at least 2037.

“Aquestive is, we believe, the first and only company that has successfully demonstrated a repeatable and predictable capability for orally administering a film for the delivery of systemic epinephrine as indicated by the results from the two completed Phase 1 PK trials with AQST-108 that will be shared at today’s R&D event,” remarked Dan Barber, Chief Operating Officer of Aquestive. “We have taken the learnings from the AQST-108 studies regarding absorption and conversion and have applied them to the development of our second generation prodrug, AQST-109. We plan to commence a Phase 1 PK trial with AQST-109 and anticipate a topline data readout in the second half of 2021.”

“Today is an exciting day for the Aquestive team,” said Keith Kendall, President and Chief Executive Officer of Aquestive. “Now that we have completed the submission of our initial patent applications, we are thrilled to provide our various stakeholders more insight into our scientific and clinical efforts to develop treatments for anaphylaxis. As we will discuss during our R&D event today, patients, caregivers, and healthcare providers remain highly interested in non-invasive routes of delivery for systemic epinephrine. Our surveys show that 80% of patients surveyed are interested in PharmFilm replacing their current medical device and 96% of patients surveyed believe that PharmFilm would be easier to administer during an emergency situation when compared to their current medical device.”

AQST-108 Sublingual FilmAquestive plans to outline in the R&D event today that its “first of its kind” oral sublingual film candidate delivering systemic epinephrine, AQST-108, is composed of the prodrug dipivefrin, which is contained within a unique polymeric matrix of Aquestive’s PharmFilm technology. Dipivefrin is currently approved by the FDA for ophthalmic indications. Dipivefrin is enzymatically cleaved systemically into epinephrine after administration.

Aquestive previously completed an initial PK trial (Protocol 180299). This study featured a single ascending dose design with between 6-12 healthy subjects completing each dosing level during Part I and Part II of the study. During the study, both PK and pharmacodynamic (PD) markers were measured. At the target dose level, the observed range for time to reach maximal concentration (Tmax) for AQST-108 was 15-35 minutes, and the observed maximal concentration (Cmax) was 1487 pg/mL. In addition, this study indicated that AQST-108 was rapidly converted to epinephrine with an observed epinephrine Tmax range of 20-60 minutes and an observed Cmax of 261 pg/mL.

Aquestive recently completed its second Phase 1 PK trial in 28 healthy adult subjects, which featured a four-treatment crossover design comparing PK, safety and pharmacodynamics of AQST-108 to that of epinephrine administered via both subcutaneous and intramuscular injections. In this study, the observed range for Tmax for AQST-108 was 10-40 minutes and the observed Cmax for AQST-108 was 1276 pg/mL. In addition, this study indicated that AQST-108 was rapidly converted to epinephrine with an observed Tmax range of 11-106 minutes and an observed Cmax of 205 pg/mL. This was compared to an epinephrine Tmax range of 4-75 minutes and 8-68 minutes and Cmax of 475 pg/mL and 388 pg/mL for the intramuscular and subcutaneous injections, respectively.

In addition, several pharmacodynamic markers were measured during the second Phase 1 PK study. AQST-108 demonstrated changes from baseline in heart rate, systolic blood pressure, and diastolic blood pressure which are relevant in the context of anaphylaxis treatment and epinephrine’s mechanism of action. For instance, for the area under the effect curve (AUEC) for systolic blood pressure, the median values for AQST-108 and intramuscular injected epinephrine were 452 and 428 (in hr*mm hg), respectively, indicating a comparable effect from both treatments on systolic blood pressure in healthy volunteers. A similar pattern was demonstrated for other pharmacodynamic measures as well.

Aquestive plans on meeting with the FDA in the second half of 2021 to review these results and discuss next steps in the development of AQST-108.

AQST-109 Sublingual FilmDuring today’s R&D event, Aquestive will articulate its development strategy for a second epinephrine prodrug candidate, AQST-109 sublingual film. AQST-109 is a next generation prodrug of epinephrine that Aquestive intends to develop for sublingual treatment of allergic reactions including anaphylaxis. In vitro tests and preclinical studies indicate that AQST-109 has the potential to absorb more extensively, convert more rapidly to systemic epinephrine, utilize less drug and provide a unique profile when compared to AQST-108. Aquestive anticipates conducting and completing a single ascending dose PK study in the second half of 2021. Based upon receiving favorable topline results from the study, Aquestive intends to request a pre-IND meeting with the FDA.

Webcast Access/ReplayA webcast of the virtual R&D event today at 9:00 am ET and accompanying slides will be available under “Events and Presentations” in the Investors section of the Company’s website at https://investors.aquestive.com/events-and-presentations. In addition, the R&D event can be accessed by dialing (833) 640-1722 from the U.S. and (602) 585-9829 internationally, followed by the conference ID: 3598556. The event webcast will be archived for 30 days.

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