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Item 1. Business

2025-03-05 compared with 2024-03-05 · 261 added, 231 removed, 388 unchanged (56% of the section changed)

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Aquestive is a pharmaceutical company advancing medicines to bring meaningful improvement to patients’ lives through innovative science and delivery technologies.

We are developing pharmaceutical products to deliver complex molecules through administrations that are alternatives to invasive and inconvenient standard of care therapies.

We are developing pharmaceutical products to deliver complex molecules through alternative administrations to invasive and inconvenient standard of care therapies.

We have a proprietary commercial product, Libervant® (diazepam) Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy between two to five years of age, which was launched in April 2024.

We are also advancing a product pipeline for the treatment of severe allergic reactions, including anaphylaxis, under the trade name "Anaphylm™", and our Adrenaverse epinephrine prodrug pipeline platform.

We have five licensed commercialized products which are marketed by our licensees in the U.S.

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We are the exclusive manufacturer of these licensed products.

Aquestive also collaborates with pharmaceutical companies to bring new molecules to market using proprietary, best-in-class technologies, like PharmFilm ® , and has proven drug development and commercialization capabilities.

We are advancing a product pipeline for the treatment of severe allergic reactions, including anaphylaxis.

We have also developed a product pipeline focused on treating diseases of the CNS.

We also collaborate with pharmaceutical companies to bring new molecules to market using proprietary, best-in-class technologies, like PharmFilm®, and have proven drug development and commercialization capabilities.

Our production facilities are located in Portage, Indiana, and our corporate headquarters and primary research laboratory facilities are based in Warren, New Jersey.

We manufacture licensed products at our facilities and anticipate that our current manufacturing capacity is sufficient for commercial quantities of our licensed products and product candidates currently in development.

We manufacture licensed products at our facilities and anticipate that our current manufacturing capacity is sufficient for commercial quantities of our proprietary and licensed products and product candidates currently in development.

Our facilities have been inspected by the FDA, TGA, and DEA and are subject to inspection by all applicable health agencies, including ANVISA and EMA.

Not all collaborative or licensed products of Aquestive that may be commercially launched in the future will necessarily be manufactured by us, such as the case with KYNMOBI.

PharmFilm – Our Oral Film Technology

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patents, and more than 150 pending patent applications worldwide.

Several of the patents in this intellectual property portfolio are utilized in each of our proprietary pipeline products.

Several of the patents in this intellectual property portfolio are utilized in each of our proprietary pipeline products and certain of these patent and patent application cover non-film applications (topical).

We are continuing to develop additional intellectual property and know-how related to the applications and engineering of PharmFilm alone or in combination with other technologies to create product capabilities that have compelling value propositions.

PharmFilm is comprised of proprietary polymer compositions that serve as film formers to hold active pharmaceutical ingredients, or APIs, and excipients in place.

PharmFilm is comprised of proprietary polymer compositions that serve as film formers to APIs and excipients in place.

Proprietary and patent-protected compositions, formulations and manufacturing techniques and technology are employed to ensure that the API is distributed uniformly throughout the film and that target absorption levels are achieved.

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• customizable taste profiles.

A drenaverse ™ – Our Epinephrine Prodrug Technology

Our Adrenaverse™ platform contains a library of over twenty epinephrine prodrug product candidates intended to control absorption and conversion rates across a variety of possible dosage forms and delivery sites.

Epinephrine plays a critical role in immune suppression but, until now, its role has been limited due to issues in the absorption and conversion of epinephrine in the human body.

We believe that our Adrenaverse platform has demonstrated the ability to harness the therapeutic potential of epinephrine through highly differentiated prodrug formulations, which can achieve absorption, provide sustained local exposure and avoid systemic exposure.

The Adrenaverse platform makes it possible to deliver epinephrine locally across mucosal surfaces and the skin and, therefore, we believe that it has the potential to yield multiple product candidates focused on treating a range of diseases.

The Company’s pipeline includes Anaphylm™ (epinephrine) Sublingual Film and AQST-108 (epinephrine) Topical Gel, which are both product candidates emerging from the Company’s Adrenaverse epinephrine prodrug platform.

Our Product Portfolio and Pipeline

The following table outlines our proprietary growth drivers and licensed products.

Sympazan ® , Zuplenz ® , PharmFilm ® and the Aquestive logo are registered trademarks of Aquestive Therapeutics, Inc.

Libervant ® , Sympazan ® , PharmFilm ® and the Aquestive logo are registered trademarks of Aquestive Therapeutics, Inc.

All other registered trademarks referenced herein are the property of their respective owners.

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Complex Molecule Portfolio

Our PharmFilm technology allows us to develop medicines that offer non-invasive delivery, customized suitability for patients with dysphagia, or trouble swallowing, can be administered without water and ensures consistent therapeutic dosing.

We believe that these characteristics will permit us to achieve the desired patient outcomes, while potentially reducing the total cost of patient care.

We have developed a proprietary pipeline of complex molecule-based product candidates as alternatives to invasively administered standard of care therapeutics addressing large market opportunities.

The active programs in our complex molecule pipeline portfolio are:

• Anaphylm (epinephrine sublingual film, pronounced “ana-film”) – the first and only non-device based, orally delivered epinephrine product candidate that has shown clinical results comparable to auto-injectors (such as EpiPen® and Auvi-Q®) for the emergency treatment of allergic reactions, including anaphylaxis.

Epinephrine is the standard of care in the treatment of anaphylaxis and is currently administered via intramuscular injection (IM) including auto-injectors, such as EpiPen and Auvi-Q, which require patients or their caregivers to inject epinephrine into the patient’s thighs during an emergency allergic reaction.

As a result of this route of administration, many patients and their caregivers are reluctant to use currently available products;

however, Anaphylm would, if approved by the FDA, allow a patient to simply place a dissolvable strip, approximately the size and weight of a postage stamp, under the tongue, providing an appropriate medication where it is needed, when it is needed and in a form preferred by patients.

We completed a first-in-human Phase 1 clinical trial for Anaphylm in Canada.

This Phase 1 randomized, single-ascending dose study was performed in order to assess the safety, tolerability, and pharmacologic profile of Anaphylm.

In February 2022, the FDA cleared our IND allowing for clinical investigation of Anaphylm in the U.S.

The FDA confirmed that the 505(b)(2) approval pathway is acceptable for the development of Anaphylm.

The FDA granted Fast Track designation in March 2022 to Anaphylm for the emergency treatment of allergic reactions, including anaphylaxis.

In February 2022, we reported positive topline data from Part 1 of our crossover study of Anaphylm, EPIPHAST, a randomized, open-label, three-part adaptive design, crossover study in healthy adult subjects comparing the PK and PD of epinephrine delivered via Anaphylm oral film compared to epinephrine IM.

The EPIPHAST study was also conducted in Canada.

In Part 1 of the EPIPHAST study, multiple oral film formulations and dosage strengths of Anaphylm were evaluated.

The lead formulation of Anaphylm has shown clinically meaningful blood concentrations when delivered in two different physical configurations, with a median time to maximum concentration (Tmax) of 13.5 minutes and 22.5 minutes, respectively.

Part 1 also showed arithmetic mean maximum concentrations (Cmax) of 771 pg/mL and 580 pg/mL for the two configurations, or geometric mean Cmax values of 258pg/mL and 268pg/mL for the two configurations, respectively.

These geometric mean Cmax and median Tmax values are consistent with those previously reported for approved injectable epinephrine devices such as EpiPen.

Under Part I of the EPIPHAST study, the healthy volunteers were also exposed to a 0.5mg IM of epinephrine, allowing for a comparison with the PK, safety, and tolerability of the higher end of the approved dosage range of epinephrine, consistent with guidance received from the FDA in a written response to our IND for Anaphylm The findings show that these two configurations of the selected Anaphylm formulation can deliver clinically meaningful blood concentrations of epinephrine sooner than that observed with the higher dose of epinephrine IM injection, and in line with existing epinephrine auto-injectors.

In addition, dosing with Anaphylm resulted in changes in blood pressure and heart rate that were comparable to epinephrine auto-injectors.

The Part I EPIPHAST study indicated that treatment was well tolerated, with no serious adverse events, significant medical events, or treatment-related severe adverse events reported.

In April 2022, we reported positive topline results from Part 2 of the EPIPHAST study for Anaphylm.

Part 2 is a randomized, crossover design comparing Anaphylm 12mg to epinephrine IM 0.3mg.

Utilizing a replicate crossover design, Part 2 confirmed in a larger population of 24 healthy subjects the key PK and PD measures observed in Part 1 of the EPIPHAST study and the first-in-human PK study.

The median Tmax was observed to be 15 minutes for Anaphylm, compared to 50 minutes for the epinephrine IM 0.3mg.

In July 2022, we reported positive topline results from the final two arms of Part 3 of the EPIPHAST study for Anaphylm.

The purpose of Part 3 was to continue to study the administration of the film under a variety of conditions to further characterize its PK, PD and safety.

The final two arms were designed to assess the impact of (1) administering the film sublingually two minutes after consuming a peanut butter sandwich and (2) swallowing the film whole immediately with water.

Part 3 study results demonstrated consistent Tmax of 12 minutes with sublingual administration of Anaphylm epinephrine oral film, after consuming a peanut butter sandwich.

Part 3 study also showed positive results with an unexpectedly high level of gastrointestinal absorption after swallowing Anaphylm whole immediately with water that was distinct from the sublingually absorbed profile.

In September 2022, we reported positive topline results from the EPIPHAST II trial for Anaphylm.

The EPIPHAST II trial was designed to compare single doses of Anaphylm to EpiPen 0.3mg and epinephrine IM 0.3mg, as well as repeat doses of Anaphylm to repeat doses of epinephrine IM 0.3mg.

Results from the single dose administration showed Anaphylm achieved a significantly faster Tmax (12 minutes), compared to both EpiPen (22.5 minutes) and epinephrine IM 0.3mg (45 minutes).

Anaphylm repeat dosing provided significantly higher drug plasma concentrations, with a Tmax of 8 minutes after administration, and extensive absorption was observed.

The mean Cmax of Anaphylm was 465 pg/mL after one dose and 2,958 pg/mL after two doses.

In comparison, the epinephrine IM 0.3mg Cmax was 489 pg/mL after one dose and 911 pg/mL after two doses.

The single dose of EpiPen resulted in a Cmax of 869 pg/mL.

Changes in systolic blood pressure and heart rate were similar after a single dose of Anaphylm when compared to a single dose of EpiPen.

This data, along with the data from the completed EPIPHAST study, was the basis for our second End-of-Phase 2 (EoP2) meeting with the FDA.

We received a positive written feedback from the FDA after our initial EoP2 meeting request to discuss Chemistry, Manufacturing, and Controls (CMC) for Anaphylm, which we believe indicates that our approach to characterizing attributes of Anaphylm appears reasonable in the context of a potential future filing.

In late December 2022, we received the final minutes from the EoP2 meeting with the FDA which provided clarity as to the FDA’s expectations regarding key program areas.

In March 2023, we obtained further clarification from the FDA indicating that we should submit our pivotal study protocol for review once it selects its reference listed drugs (RLDs).

We have completed additional studies that have identified the appropriate auto-injector RLDs and continue to work on the optimal administration parameters.

In April 2023, the FDA conditionally accepted the proprietary name Anaphylm as the proposed brand name for Anaphylm.

• Anaphylm (epinephrine) Sublingual Film – the first and only non-device based, orally delivered epinephrine product candidate in development that has shown clinical results comparable to auto-injectors (such as EpiPen ® and Auvi-Q ® ) for the emergency treatment of allergic reactions, including anaphylaxis.

Epinephrine is the standard of care in the treatment of anaphylaxis and is typically administered via intramuscular injection (IM), including manual auto-injectors such as EpiPen and Auvi-Q, which require patients or their caregivers to inject epinephrine into the patient’s thigh during an emergency allergic reaction.

As a result of this route of administration, many patients and their caregivers are reluctant to use injectable products.

In August 2024, a nasal spray device was approved by the FDA for the treatment of severe allergic reactions, including anaphylaxis.

However, Anaphylm would, if approved by the FDA, allow a patient to simply place a dissolvable strip, approximately the size and weight of a postage stamp, under the tongue, providing an appropriate medication where it is needed and when it is needed.

The FDA conditionally accepted the proprietary name Anaphylm™ (pronounced “ana-film”) as the proposed brand name for Anaphylm.

Final approval of the Anaphylm proprietary name is conditioned on FDA approval of Anaphylm, if any.

In May 2023, we reported positive results from the latest clinical studies evaluating PK and PD performance of Anaphylm.

The time to maximum blood concentration (median Tmax) for Anaphylm was 10 minutes with a range of 5-20 minutes.

Early drug exposure at 10 minutes for Anaphylm was similar to epinephrine manual injection and over 4

times higher than epinephrine manual injector.

PD effects were observed as early as 2 minutes for both Anaphylm and the auto-injectors.

In July 2023 we released topline data from the latest clinical crossover pilot trial, Study AQ109103 (the “103 Study”), for Anaphylm.

The 103 Study demonstrated that Anaphylm, using the expected finalized dosing administration instructions, delivers epinephrine systemically as effectively as either commercially available autoinjectors or the manual intramuscular (IM) injection.

Administration of Anaphylm 12mg resulted in a geometric mean maximum epinephrine concentration (Cmax) of 457 pg/mL and a median time to maximum concentration (Tmax) of 15 minutes after administration.

The partial Area Under the Curve measurement, or pAUC, was bracketed between previously generated manual 0.3mg IM injection and epinephrine 0.3mg autoinjector data at all time points between 10 and 60 minutes, post-dosing.

Importantly, Anaphylm 12mg met the standards of bracketing in the 103 Study for all the critical parameters that we anticipate measuring in the pivotal PK study, including Cmax and pAUC during the critical early time periods, while remaining similar to autoinjectors for Tmax.

The 103 Study also included crossover arms of Anaphylm 12mg with alternate dosing instructions as well as Anaphylm 14mg with the finalized dosing instructions.

In all cases in the 103 Study, the product was considered safe and well-tolerated with no serious adverse events.

We recently received comments from the FDA on the pivotal Phase 3 PK clinical study protocol for Anaphylm we submitted.

In its comments, the FDA indicated that our proposed endpoints, sample size, and statistical analysis are reasonable.

As anticipated, the FDA also reminded is that PK sustainability post-dosing (30–60 minutes) is an important factor and recommended using repeat-dose data to support PK sustainability.

In December 2023, the first patient was dosed in the initial Phase 3 pivotal Pharmacokinetic (PK) clinical study of Anaphylm (epinephrine).

The two-part, Phase 3, single-center, open-label, randomized study is designed to compare the PK and pharmacodynamics (PD) of single and repeat doses of Anaphylm versus single and repeat doses of the epinephrine IM injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in healthy adult subjects.

The primary objective is to compare the PK of epinephrine following the single administration of Anaphylm to single administration of epinephrine IM injection in healthy adult subjects.

The secondary objectives include evaluating PK sustainability following repeat administration and evaluating the safety and tolerability following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors.

A comprehensive adult and pediatric Human Factors program, an expected and ongoing part of the Anaphylm clinical development program, will also be included in the Anaphylm NDA to support future labeling and the use of the product by intended patients.

• AQST-108 (sublingual film) – AQST-108 is composed of the prodrug dipivefrin which is enzymatically cleaved into epinephrine after administration.

Dipivefrin is currently available outside of the U.S.

for ophthalmic indications.

A sublingual film formulation delivering systemic epinephrine has been developed by Aquestive for the treatment of conditions other than anaphylaxis.

Based on topline results of a prior Phase 1 PK trial in 28 healthy adult volunteers conducted by Aquestive, AQST-108 was generally well-tolerated, with systemic adverse events observed that are consistent with the known adverse events profile for epinephrine.

• Adrenaverse - (epinephrine prodrug platform) – Additional indications and delivery methods are currently being explored under our epinephrine prodrug platform, which we have branded as Adrenaverse.

We have completed an initial formulation of an AQST-108 topical product using the Adrenaverse platform and plan on testing this formulation in humans in the coming months.

Based on in-vitro data, we have seen rapid absorption of AQST-108 across porcine skin tissue.

Although epinephrine is a vasoconstrictor and does not penetrate well through the skin, we believe that the Adrenaverse platform may allow for topical absorption, thereby creating the potential treatment for a variety of dermatological condition.

Upon completion of the preclinical and feasibility work relating to this program, we expect to request a pre-IND meeting for Adrenaverse with the FDA and plan to disclose the indication and path forward for development, once we have received feedback from the FDA.

Proprietary CNS Product Candidate

On February 24, 2022, following a Phase 1 clinical study conducted by the Company outside of the U.S., the FDA cleared our IND for Anaphylm, allowing for clinical investigation of Anaphylm in the U.S.

The FDA confirmed that the 505(b)(2) regulatory approval pathway is acceptable for the development of Anaphylm.

The FDA granted Fast Track designation of Anaphylm in March 2022.

Throughout 2022 and 2023, we reported positive topline data from several clinical studies evaluating multiple oral film formulations and dosage strengths of Anaphylm in healthy adult subjects, including cross over studies comparing the PK and PD of epinephrine delivered via Anaphylm compared to current standards of care, EpiPen and IM injectors.

These studies demonstrated that treatment with Anaphylm was well tolerated, with no serious adverse events, significant medical events, or treatment-related severe adverse events reported.

The data from these clinical studies formed the basis for the EoP2 meeting with the FDA in December of 2022, which provided clarity as to the FDA’s

expectations regarding key clinical program areas for design of revised dosing instructions expected for use in our pivotal clinical trial.

In the fourth quarter of 2023, we received comments from the FDA on the protocol for our pivotal clinical study for Anaphylm, which comments indicated that our proposed endpoints, sample size, and statistical analysis for the proposed pivotal clinical study were reasonable and provided clarity on PK sustainability with repeat-dose requirements.

We incorporated the FDA’s feedback into the pivotal clinical study design, which study commenced in in the fourth quarter of 2023.

In January 2024, we completed a Type C meeting with the FDA in which the FDA found that we had adequately addressed the FDA’s previous concerns noted in the EoP2 meeting, including addressing (1) the impact of any product hold time, (2) the potential for emesis (vomiting), and (3) the impact of potential mouth conditions such as angioedema (swelling), by removing product hold time from the administration instructions and providing additional information on how to characterize emesis in our NDA submission with the FDA.

Regarding mouth conditions, the FDA recommended administering Anaphylm after oral exposure to a known allergen and assessing PK performance thereunder.

This study replaced our previously planned angioedema study.

In those comments, the FDA did not outline any new clinical development requirements for the Anaphylm program.

The FDA reserved judgement on the sufficiency of the Anaphylm clinical development program until completion of ongoing and planned studies, the results of which were presented at a pre-NDA interaction with the FDA on November 22, 2024.

In March 2024, we released topline data from our pivotal clinical study for Anaphylm.

The two-part, Phase 3, single-center, open-label, randomized study was designed to compare the PK and PD of single and repeat doses of Anaphylm versus single and repeat doses of the IM injection and epinephrine autoinjectors (EpiPen® and Auvi-Q®) in healthy adult subjects.

The results of this study demonstrated that the primary endpoint of epinephrine PK biocomparability of the single administration of Anaphylm to the single administration of Adrenalin (epinephrine IM injection) and epinephrine autoinjectors in healthy adult subjects was met, as well as the secondary endpoints, which included evaluating the PK sustainability of Anaphylm following repeat administration and the safety and tolerability of Anaphylm following single and repeat administrations versus epinephrine IM injection and epinephrine autoinjectors.

I n June 2024, we reported positive topline PK data from the Company's temperature / pH study of Anaphylm.

The single-dose, five-period, randomized crossover study was designed to compare the PK and PD of Anaphylm just after consuming normal water at different temperatures (hot, cold, and room temperature) as well as water of different pHs (acidic- lemon water, and basic- baking soda water).

The most consumed beverages, such as soda, milk, coffee, and juice, have acidity between lemon water and normal water.

The primary PK parameters were the maximum amount of epinephrine measured in plasma (Cmax) and exposure, or the area under the curve (AUC), at predefined time points after dosing, in 30 healthy adult subjects.

Topline PK and PD data from the study showed no statistically significant difference in PK and PD results between the different groups based on temperature and pH variability in the mouth.

In July 2024, we reported positive topline data from the self-administration PK study of Anaphylm.

The single-dose, three-period, randomized crossover study was designed to compare the PK and PD of Anaphylm self-administered, Anaphylm healthcare provider (HCP)-administered, and Adrenalin IM injection HCP- administered.

The primary PK parameters were the Cmax and the AUC exposures, at predefined time points after dosing in 36 healthy adult subjects.

The median time to maximum concentration (Tmax) was 15 minutes for both the Anaphylm self-administered and HCP-administered arms, while the median Tmax for the Adrenalin IM injection HCP-administered arm was 50 minutes post-administration.

Also, there was no statistical difference between the Anaphylm self-administered and HCP- administered arms of the study based on a comparison of epinephrine exposures across the first 60 minutes post-administration.

Topline PD data from the study showed no difference in the median increase in systolic blood pressure, diastolic blood pressure, and heart rate whether Anaphylm was self-administered or HCP-administered.

In October 2024, we reported positive topline data from an oral allergy syndrome challenge study (now referred to as the "OASIS" study), meeting both primary and secondary endpoints.

The two-part study demonstrated that Anaphylm's PK and PD profile during allergen-induced oral physiological changes was consistent with its profile without an allergen challenge.

In addition, following allergen exposure where 94% of subjects exhibited moderate to severe symptoms per the predefined oral severity score, rapid symptom resolution was observed beginning as early as 2 minutes post-administration.

The median time to complete symptom resolution was 12 minutes compared to 74 minutes at screening baseline, with 50% of all symptoms across all subjects resolving by 5 minutes.

The mean time of symptom resolution for edema, which affected approximately 25% of subjects, was 5 minutes after Anaphylm administration.

The PK profile remained consistent, with median Tmax maintained at 12 minutes and comparable Cmax values between allergen-exposed and non-exposed cohorts.

The safety profile was favorable, with all adverse events classified as mild to moderate and resolving without medical intervention.

Also in October 2024, at the ACAAI 2024 Annual Meeting in Boston, we presented results from a subsequent analysis of our pivotal study data demonstrating Anaphylm's consistent PK and PD profile regardless of variable placement or intraoral movement.

The analysis showed that 87.5% of subjects maintained consistent film placement during disintegration.

In the 12.5% of subjects where movement was noted, there were no significant differences in Cmax and Tmax.

These findings further demonstrate that initial placement or subsequent movement of the sublingual film had no impact on epinephrine PK or PD comparability to epinephrine autoinjectors.

On November 22, 2024, we received positive pre-NDA written response feedback from the FDA prior to our planned NDA submission in the first quarter of 2025.

The FDA did not indicate in those responses that any additional adult clinical trials would be necessary for submitting the NDA for Anaphylm.

In addition, the FDA agreed with our planned NDA content and format for the submission, planned safety evaluation, and planned pediatric trial.

The FDA also provided further guidance on additional data views to be included in the planned NDA submission and continued to emphasize its focus on PK sustainability for a single dose.

In addition, the FDA requested minor modifications to the pediatric trial protocol which requested modifications were incorporated in the final pediatric trial protocol.

Finally, the FDA noted that due to the new route of administration and the data supporting this route of administration, an advisory committee meeting may be necessary prior to FDA approval and we are preparing for this potential request from the FDA.

We commenced the NDA submission to the FDA in the first quarter of 2025.

The pediatric study in subjects from the ages of 7 to 17 (weight greater than or equal to 30 kgs) is currently underway and the initial study results appear in line with expectations.

We are planning on initiating a product launch of Anaphylm, if approved by the FDA, in the first quarter of 2026.

This is based on completing the NDA submission with the FDA in the coming weeks.

• AQST-108 (epinephrine) Topical Gel – Our product candidate, AQST‑108 is composed of the prodrug dipivefrin which is enzymatically cleaved into epinephrine after administration.

AQST‑108, is a topically delivered adrenergic agonist prodrug, which we believe has the potential to support the re-establishment of immune privilege in the hair follicle and we are pursuing its development for the treatment of alopecia areata, which is an autoimmune disease leading to hair loss on the scalp, face and, in more severe cases, other body areas.

We completed the first human clinical trial for AQST-108.

The two-part trial was designed to assess the safety and local tolerability of AQST-108.

Part 1 was designed as a single ascending dose escalation study to assess the safety and PK of five different dose levels.

The 1.0% dose of AQST-108 was chosen based on the down selection from the highest dose to move into the Part 2 study of the development program.

In Part 2, three formulations based on excipient variations were evaluated in twelve healthy subjects.

In Parts 1 and 2, no serious adverse events or topical adverse events were observed.

In Part 2, the calculated percentage of AQST-108 observed in the skin remained consistent across all studied formulations and zero post-dose AQST-108 concentrations in plasma were observed.

We received pre-IND FDA feedback in the fourth quarter of 2024 to align on the Phase 2a clinical trial design and plan to open and IND and initiate the Phase 2a clinical trial in the second quarter of 2025.

Proprietary CNS Product

We believe the application of our proprietary PharmFilm ® technology is particularly valuable and relevant to patients suffering from certain CNS disorders to meet patients’ unmet medical needs and to solve patients’ therapeutic problems.

We believe there remains a significant opportunity to develop additional products in the CNS market.

Additionally, our know-how and proprietary position have broad application beyond CNS, and we plan to explore the applications of PharmFilm in other disease areas.

Our most advanced asset within our proprietary CNS portfolio, focused in epilepsy, is as follows:

• Libervant – a buccally, or inside of the cheek, administered soluble film formulation of diazepam is our most advanced proprietary investigational product candidate.

Aquestive developed Libervant as an alternative to device-dependent rescue therapies currently available to patients with refractory epilepsy, which are a rectal gel and nasal sprays.

In August 2022, the FDA granted tentative approval for Libervant for the acute treatment of intermittent,

stereotypic episodes of frequent seizure activity ( i.e ., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.

The FDA has concluded that Libervant has met all required quality, safety, and efficacy standards for approval.

Due to an existing FDA regulatory grant of orphan drug market exclusivity for Valtoco®, a diazepam nasal spray product sold by another company for use in patients 12 years of age and older, the FDA has determined that Libervant is not yet eligible for marketing in the United States.

As a result of this determination, the FDA cannot give final approval for Libervant until the expiration of the orphan drug market exclusivity in January 2027.

In June 2023, we filed an NDA for Libervant for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity ( i.e.

, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy between two and five years of age.

The FDA accepted the filing for review and assigned a PDUFA goal date of April 28, 2024.

Diastat ® (diazepam) rectal gel is the only treatment currently available to this age group of patients for this indication.

There is no assurance that, if the pediatric NDA for Libervant is approved by the FDA, it will overcome the orphan drug exclusivity granted by the FDA for Valtoco and be granted U.S.

market access for this patient age group.

Further, there can be no assurance that another company will not obtain other FDA market exclusivity that blocks U.S.

market access for Libervant for any age group in this patient population.

See “Licensed Commercial Products and Product Candidates and Other Products – Libervant” for a discussion of the licensing arrangement for this product candidate.

• Libervant – a buccally, or inside of the cheek, administered soluble film formulation of diazepam, Libervant was developed as an alternative to device-dependent rescue therapies currently available to patients with refractory epilepsy, which are a rectal gel and nasal sprays.

On April 26, 2024, the FDA approved Libervant for U.S.

market access for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity ( i.e.

, seizure clusters, acute repetitive seizures) (or ARS) that are distinct from a patient’s usual seizure pattern in patients with epilepsy between two to five years of age.

Libervant is the first and only orally administered rescue product for the treatment of seizure cluster in patients between ages two to five.

The only other current FDA approved product for these ARS patients between two to five years of age is a diazepam rectal gel.

In October 2024, Libervant 5mg, 7.5mg, 10mg, 12.5mg and 15 mg for ARS patients between two and five years of age became available through multiple retail distribution channels.

Market access activities have broadened coverage.

Libervant is available nationwide with retail distribution capabilities in place.

For Medicaid patients, Libervant is available in all states.

Commercial patient access to Libervant continues to expand based on health plan reviews and Pharmacy Benefit Manager agreements.

Prior to the FDA approval of Libervant for ARS patients between two to five years, the FDA granted tentative approval in August 2022 for Libervant for the same indication in patients with epilepsy 12 years of age and older, finding that Libervant had met all required quality, safety, and efficacy standards for approval.

However, due to an existing FDA regulatory grant of orphan drug market exclusivity for a diazepam nasal spray product sold by another

company for use in ARS patients 6 years of age and older, the FDA determined that Libervant was not yet eligible for marketing in the United States for this patient population of 12 years of age and older.

We expect to file for FDA approval for use of Libervant for these ARS patients aged between 6 and 12 years prior to the expiration of the orphan drug marketing exclusivity block of the nasal spray product.

As a result of the orphan drug marketing exclusivity granted by the FDA to the nasal spray product, the FDA cannot give final approval for U.S.

market access for Libervant for any age group of 6 and above until the expiration or inapplicability of the orphan drug market exclusivity.

However, overcoming the orphan drug marketing exclusivity determination is difficult to establish, with limited precedent, and there can be no assurance that the FDA will agree with our position seeking to overcome such market exclusivity and approve Libervant for U.S.

market access for this age group of 6 years and older earlier than January 2027, the scheduled date for expiration of orphan drug market exclusivity for the FDA nasal spray product.

See “Licensed Commercial Products, Product Candidates and Other Products – Libervant” for a discussion of the licensing arrangement for Libervant.

In the fourth quarter of 2024 the FDA granted seven years of ODE to Libervant® (diazepam) Buccal Film for ARS patients between two to five years of age.

Libervant was originally granted Orphan Drug Designation on November 10, 2016 and the ODE now granted to Libervant for patients ages two to five extends to April of 2031.

On February 14, 2025, in a lawsuit brought by Neurelis, Inc.

("Neurelis") against the FDA (Neurelis, Inc.

Califf, for which the Company joined as a Defendant Intervenor) challenging the FDA's approval of Libervant for ARS patients aged between two and five years, the U.S.

District for the District of Columbia issued a final appealable order entering a judgment in favor of Neurelis's motion for summary judgement and vacating the FDA’s approval of Libervant.

The District Court's ruling was not based on grounds of safety or efficacy of Libervant, but rather on the grounds that the law granting ODE to the FDA approved nasal spray Valtoco for patients aged six and older should be interpreted to extend to children aged two to five, despite that Valtoco was not approved by the FDA to treat these younger patients.

The Company is appealing this ruling and has filed a motion to stay the court's ruling pending the outcome of the appeal.

The Company is continuing to market and sell Libervant in the ordinary course, pending a final non-appealable ruling in this matter.

On February 24, 2025, Aquestive filed a request with the FDA that the FDA also confirms approval of Libervant for ARS patients aged between two and five years on the FDA regulatory grounds of clinical superiority over the other currently existing FDA approved ARS drugs, including confirming the FDA grant of ODE for Libervant for ARS patients aged between two and five years.

FDA’s orphan drug regulations define a “clinically superior” drug as “a drug shown to provide a significant therapeutic advantage over and above that provided by an approved orphan drug (that is otherwise the same drug)” in one of three ways:

the basis of greater efficacy or safety, or providing a major contribution to patient care.

While the Company is not able to determine or predict the ultimate outcome of these proceedings or provide a reasonable estimate or range of estimates of the possible outcome in these matters, the Company intends to vigorously defend against any decision that jeopardizes the on-label patient access to Libervant.

See Part II, Item 8.

Financial Statements and Supplementary Data, Note 23, Contingencies.

Licensed Commercial Products and Product Candidates and Other Products

Our portfolio also includes other products and product candidates that we have licensed, or will seek to license, or for which we have licensed our intellectual property for commercialization.

In the years ended December 31, 2023 and 2022, our licensed product portfolio generated $50.6 million and $47.7 million in revenue to Aquestive, respectively.

In the years ended December 31, 2024 and 2023, our licensed product portfolio generated $57,561 and $50,583 in revenue to Aquestive, respectively.

Those products include:

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As of December 31, 2024, Suboxone branded products retain approximately 27% film market share as generic film-based products have penetrated this market.

We have filed patent infringement lawsuits against certain companies relating to generic film-based products for buprenorphine-naloxone.

More details regarding these lawsuits are described in Part II Item 8.

Financial Statements and Supplementary Data, Note 22, Contingencies , contained herein.

• Exservan ® – an oral film formulation of riluzole, has been developed by Aquestive for the treatment of ALS.

We believe that Exservan can bring meaningful assistance to patients who are diagnosed with ALS and face difficulties swallowing traditional forms of medication.

• Emylif ® – an oral film formulation of riluzole, has been developed by Aquestive for the treatment of ALS.

We believe that Emylif can bring meaningful assistance to patients who are diagnosed with ALS and face difficulties swallowing traditional forms of medication.

This product was originally approved and marketed in the U.S.

under the name Exservan.

Exservan was approved by the FDA on November 22, 2019.

During the fourth quarter of 2019, we announced the grant of a license to Zambon for the development and commercialization of Exservan in the for the treatment of ALS.

We submitted a request for voluntary withdrawal of the NDA as the product is no longer marketed in the U.S.

and the NDA was officially withdrawn on February 14, 2025.

During the fourth quarter of 2019, we announced the grant of a license to Zambon for the development and commercialization of Exservan in the EU for the treatment of ALS which it markets as Emylif ® .

Zambon is a multinational pharmaceutical company with a focus on the CNS therapeutic area.

Under the terms of the license agreement with Zambon, an upfront payment was paid to Aquestive for the development and commercialization rights of Exservan in the EU, and Aquestive will be paid development and sales milestone payments and low double-digit royalties on net sales of the product in the EU, marketed as Emylif by Zambon.

Zambon is responsible for the regulatory approval and marketing of Exservan in the countries where Zambon seeks to market the product, and Aquestive is responsible for the development and manufacture of the product.

During the fourth quarter of 2022, Aquestive received a $0.5 million milestone payment in connection with the receipt of regulatory approval for Exservan pursuant to the terms of the license agreement with Zambon.

During the second quarter of 2023, Aquestive received a $0.5 million milestone payment in connection with the first commercial sale in the first country in the licensed territory for Exservan pursuant to the terms of the license agreement with Zambon.

In January 2021, we announced that we granted an exclusive license to MTHA for the commercialization in the United States of Exservan.

MTHA is a multinational pharmaceutical company with a focus on patients with ALS.

The product was launched by MTHA in June 2021.

Under the terms of the MTHA license agreement, Aquestive is the exclusive manufacturer and supplier of Exservan for MTHA in the United States.

Exservan may potentially fulfill a critical need for ALS patients, given it can be administered safely and easily, twice daily, without water.

In March 2022, we announced the grant of an exclusive license to Haisco for them to develop and commercialize Exservan for the treatment of ALS in China.

Under the terms of the license agreement with Zambon, an upfront payment was paid to Aquestive for the development and commercialization rights of Emylif in the EU, and Aquestive will be paid development and sales milestone payments and low double-digit royalties on net sales of the product in the EU.

Zambon is responsible for the regulatory approval and marketing of Emylif in the countries where Zambon seeks to market the product and Aquestive is responsible for the development and manufacture of the product.

During the second quarter of 2023, Aquestive received a $0.5 million milestone payment in connection with the first commercial sale in the first country in the licensed territory for Emylif pursuant to the terms of the license agreement with Zambon.

In January 2021, we announced that we granted an exclusive license to MTPA for the commercialization in the United States of Exservan.

MTPA is a multinational pharmaceutical company with a focus on patients with ALS.

The product was launched by MTPA in June 2021.

Under the terms of the MTPA license agreement, Aquestive was the exclusive manufacturer and supplier of Exservan for MTPA in the United States.

.In June 2024, the Company and MTPA mutually agreed to terminate the MTPA Licensing Agreement.

See Part II Item 8.

Financial Statements and Supplementary Data, Note 7, Material Agreements for details.

In March 2022, we announced the grant of an exclusive license to Haisco for Haisco to develop and commercialize Exservan for the treatment of ALS in China.

Haisco is a China-based public pharmaceutical company.

Haisco will lead the regulatory and commercialization activities for Exservan in China.

Aquestive will serve as the exclusive sole manufacturer and supplier for Exservan in China.

Under the terms of license agreement with Haisco, as amended, Aquestive received a $7.0 million upfront payment in September 2022, and will receive regulatory milestone

payments, double-digit royalties on net sales of Exservan in China, and earn manufacturing revenue upon the sale of Exservan in China.

• KYNMOBI ® – a sublingual film formulation of apomorphine, which is a dopamine agonist, was developed to treat episodic off-periods in Parkinson’s disease.

We licensed our intellectual property to Cynapsus Therapeutics, Inc., a company that was acquired by Sunovion for the commercialization of KYNMOBI under an Agreement dated April 1, 2016, as amended by the Sunovion License Agreement.

KYNMOBI was approved by the FDA on May 21, 2020 and commercially launched by Sunovion in September 2020.

On November 3, 2020, we entered into the Monetization Agreement with MAM Pangolin Royalty, LLC, an affiliate of Marathon.

Under the terms of the Monetization Agreement, we sold all of our contractual rights to receive royalties and milestone payments due under the Sunovion License Agreement related to Sunovion’s apomorphine product, KYNMOBI.

In June 2023, Sunovion announced that it has voluntarily withdrawn KYNMOBI from the U.S.

and Canadian markets, therefore, we likely will not receive any of the additional contingent payments under the Monetization agreement.

• Zuplenz ® – an oral soluble film formulation of ondansetron, a 5-HT antagonist, was developed for the treatment of nausea and vomiting associated with chemotherapy and post-operative recovery.

Haisco lead the regulatory and commercialization activities for Exservan in China.

Aquestive was the exclusive sole manufacturer and supplier for Exservan in China.

Under the terms of the license agreement with Haisco, as amended, Aquestive received a $7.0 million upfront payment in September 2022, and was to receive regulatory milestone payments, double-digit royalties on net sales of Exservan in China, and earn manufacturing revenue upon the sale of Exservan in China.

In June 2024, Aquestive and Haisco mutually agreed to terminate the Haisco Agreement.

See Part II Item 8.

Financial Statements and Supplementary Data, Note 7, Material Agreements for details.

• Ondif ® – an oral soluble film formulation of ondansetron, a 5-HT antagonist, was developed for the treatment of nausea and vomiting associated with chemotherapy and post-operative recovery.

Ondansetron is available as branded and generic products as intravenous injections, intramuscular injections, orally dissolving tablets, oral solution tablets, and film.

We licensed commercial rights for Zuplenz to Hypera in Brazil (which Hypera markets as Ondif).

Hypera received approval to market Zuplenz in Brazil from ANVISA on February 21, 2022.

We received a $0.9 million milestone payment in connection with this transaction.

We licensed commercial rights for Zuplenz to Fortovia (previously Midatech Pharma PLC) in the United States, Canada, and China.

Fortovia launched Zuplenz in the United States in 2015.

We had been the sole and exclusive manufacturer of Zuplenz for Fortovia.

On August 31, 2020 Fortovia filed a Chapter 11 bankruptcy proceeding in the Bankruptcy Court for the Eastern District of North Carolina.

On January 29, 2021, the Bankruptcy Court approved an agreement pursuant to which the license and supply agreement between Aquestive and Fortovia was terminated, and all rights to commercialize Zuplenz returned to us, effective January 30, 2021.

• Azstarys TM – an FDA-approved, once-daily product for the treatment of ADHD in patients age six years or older.

AZSTARYS consists of serdexmethylphenidate, a prodrug of d-methylphenidate (d-MPH), co-formulated with immediate release d-MPH.

In March 2012, we entered into an agreement with Zevra to terminate a Collaboration and License Agreement entered into by Aquestive and Zevra in April 2011.

Under this termination arrangement, we have the right to participate in any and all value that Zevra may derive from the commercialization or any other monetization of KP-415 and KP-484 compounds or their derivatives.

Among these monetization transactions are those related to any business combinations involving Zevra and collaborations, royalty arrangements, or other transactions from which Zevra may realize value from these compounds, including the product Azstarys.

On March 2, 2021, Zevra announced FDA approval of Azstarys for the treatment of ADHD.

During the year ended December 31, 2023, we recorded $1.5 million as milestone revenues for Zevra.

• Libervant TM - a buccal film formulation of diazepam tentatively approved by the FDA for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity ( i.e ., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.

We entered into the Pharmanovia Agreement with Pharmanovia, effective as of September 26, 2022, pursuant to which we granted Pharmanovia an exclusive license to certain of our intellectual property to develop and commercialize Libervant for the treatment of prolonged or acute, convulsive seizures in all ages in certain countries of the Territory during the term of the Pharmanovia Agreement.

Under the Pharmanovia Agreement, Pharmanovia will lead the regulatory and commercialization activities for Libervant in the Territory and we will serve as the exclusive sole manufacturer and supplier of Libervant in the Territory.

We licensed commercial rights for this product to Hypera in Brazil (which Hypera markets as Ondif).

Hypera received approval to market Ondif in Brazil from ANVISA on February 21, 2022.

Aquestive manufactures and supplies Ondif to Hypera.

This product was originally approved and marketed in the U.S.

under the name Zuplenz®.

We submitted a request for voluntary withdrawal of the NDA for Zuplenz, as the product is no longer marketed in the U.S.

In November 2024, the request for FDA withdrawal of the NDA for Zuplenz was completed.

• Libervant ® – We entered into the Pharmanovia Agreement with Pharmanovia, effective as of September 26, 2022, pursuant to which we granted Pharmanovia an exclusive license to certain of our intellectual property to develop and commercialize Libervant for the treatment of prolonged or acute, convulsive seizures in all ages in certain countries of the Territory, as defined in the Pharmanovia Agreement, during the term of the Pharmanovia Agreement.

Under the Pharmanovia Agreement, Pharmanovia will lead the regulatory and commercialization activities for Libervant in the Territory and Aquestive will serve as the exclusive sole manufacturer and supplier of Libervant in the Territory.

We received $3.5 million upon agreement execution.

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We commercially launched Sympazan in December 2018.

On October 26, 2022, we entered into a License Agreement with Otter Pharmaceuticals, LLC, a subsidiary of Assertio, a specialty pharmaceutical company offering differentiated products to patients, pursuant to which we granted an exclusive, worldwide license of its intellectual property for Sympazan to Assertio during the term of that agreement for an upfront payment of $9.0 million.

Additionally, in November 2022, we received a $6.0 million milestone payment upon its receipt of a notice of allowance from the United States Patent and Trademark Office of its patent application

On October 26, 2022, we entered into a License Agreement with Otter Pharmaceuticals, LLC, a subsidiary of Assertio Holdings, Inc., pursuant to which we granted an exclusive, worldwide license of its intellectual property for Sympazan to Assertio during the term of that agreement for an upfront payment of $9.0 million.

Additionally, we subsequently received from Assertio a $6.0 million milestone payment upon its receipt of a notice of allowance from the United States Patent and Trademark Office of its patent application U.S.

16/561,573, and payment of the related allowance fee.

We are the exclusive sole manufacturer and supplier of Sympazan for Assertio and will receive manufacturing fees from Assertio for the product through the expiration of such supply agreement.

We are the exclusive sole manufacturer and supplier of Sympazan for Assertio.

Aquestive is the exclusive sole manufacturer and supplier of Sympazan for Assertio and will receive manufacturing fees from Assertio for the product through the expiration of such License Agreement.

• KYNMOBI ® – a sublingual film formulation of apomorphine, which is a dopamine agonist, was developed to treat episodic off-periods in Parkinson’s disease.

We licensed our intellectual property to Cynapsus Therapeutics, Inc., a company that was acquired by Sunovion for the commercialization of KYNMOBI under the Sunovion License

KYNMOBI was approved by the FDA on May 21, 2020 and commercially launched by Sunovion in September 2020.

On November 3, 2020, we entered into the Monetization Agreement.

In June 2023, Sunovion announced that it had voluntarily withdrawn KYNMOBI from the U.S.

and Canadian markets.

See Part II Item 8.

Financial Statements and Supplementary Data, Note 17, Sale of Future Revenue for details.

• Azstarys ® – an FDA-approved, once-daily product for the treatment of ADHD in patients age 6 years or older.

AZSTARYS consists of serdexmethylphenidate, a prodrug of d-methylphenidate (d-MPH), co-formulated with immediate release d-MPH.

In March 2012, we entered into an agreement with Zevra (formerly KemPharm, Inc.) to terminate a Collaboration and License Agreement entered into by the Company and Zevra in April 2011.

On March 2, 2021, Zevra announced FDA approval of Azstarys for the treatment of ADHD.

Pursuant to the terms of the March 2012 agreement with Zevra, we began to receive milestone and royalty revenues for Azstarys.

See Part II Item 8.

Financial Statements and Supplementary Data, Note 7, Material Agreements for details.

Market Overview

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Anaphylaxis is a potentially life-threatening systemic allergic reaction, with an estimated incidence of 50 to 112 episodes per 100,000 people per year.

An international study found that hospital admissions for anaphylaxis has increased over a 15-year study period.

An international study found that hospital admissions for anaphylaxis have increased over a 15-year study period.

The most common causes of reactions that can include anaphylaxis are medications, foods (such as peanuts), and venom from insect stings.

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Auto-injectors can be inconvenient to transport and many patients and caregivers dislike injections as a delivery method.

In August 2024, a non-injection-based epinephrine delivery device, Neffy ®, was approved by the FDA and EMA for the treatment of severe allergic reactions, including anaphylaxis, and is in the early phase of its commercial launch.

Proper dosing and the ability to effectively administer epinephrine in a timely, reliable manner is critical for patients experiencing anaphylaxis.

However, we believe that the inability to administer complex molecules via oral administration has limited the development of treatments that have the potential to provide significant patient benefit.

We designed Anaphylm, a “first of its kind” oral sublingual film formulation delivering systemic epinephrine, as a rescue medicine for the treatment of anaphylaxis, using Aquestive’s proprietary PharmFilm technologies, to improve patient compliance and lower the total cost of care.

We believe there is a significant market opportunity for a non-injectable, easier to administer product with a fast onset of action.

We believe there is a significant market opportunity for a non-injectable, device-free, easier to administer product with a fast onset of action.

A product with this profile could enable patients to conveniently and rapidly self-administer a reliable and accurate dose of epinephrine during an anaphylactic reaction, which we believe will improve patient compliance.

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Chronic medicines are used on a daily basis to suppress seizure activity.

Approximately 1.1 million of those suffering from epilepsy will continue to suffer with breakthrough seizures and may require an acute (rescue) management strategy.

Approximately 1.1 million of those suffering from epilepsy will continue to suffer

with breakthrough seizures and may require an acute (rescue) management strategy.

Patients are routinely prescribed antiepileptic drugs, or AEDs, as “maintenance” therapy to control chronic seizure activity.

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One of the most effective benzodiazepines currently available for the treatment of acute seizures is diazepam.

Diazepam has historically been marketed as a product administered rectally and more recently, a nasal spray product was introduced to the market.

Diazepam has historically been marketed as a product administered rectally and more recently, a nasal spray product was introduced to the market for patients ages 6 years and up.

Rectal administration of this drug presents a particular challenge for patients.

We developed our product candidate Libervant as an alternative to the device-dependent rescue therapies currently available to patients with refractory epilepsy.

We developed our product candidate Libervant as an alternative to the device-dependent rescue therapies currently available to patients with refractory epilepsy and Libervant® is currently available for patients between ages two to five.

See “Our Product Portfolio and Pipeline” above and “Competition” below in this Item 1.

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Manufacturing and Product Supply

We operate two manufacturing and primary packaging facilities located in Portage, Indiana, where we currently manufacture our licensed products, Suboxone, Exservan, Ondif and Sympazan, on an exclusive basis.

These facilities are expected to have a combined capacity to accommodate the production of our proprietary product pipeline candidates and licensed products, without any current need for additional infrastructure.

We operate two manufacturing and primary packaging facilities located in Portage, Indiana, where we currently manufacture our licensed products, Suboxone, Emylif, Ondif and Sympazan, and our proprietary product, Libervant for patients between two to five years of age, on an exclusive basis.

These facilities are expected to have a combined capacity to accommodate the production of our proprietary product pipeline candidate and licensed products, without any current need for additional infrastructure.

In 2022, we completed work to expand our manufacturing capabilities to include serialization and secondary packaging.

This expansion allows us to support our existing and possible future business collaborations more broadly.

With the cGMP facilities in Indiana, we will continue to explore possible additional manufacturing capabilities in 2023.

With the cGMP facilities in Indiana, we will continue to explore possible additional manufacturing efficiencies in 2025.

We will also continue to consider our anticipated facilities and infrastructure needs as our product development grows.

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This industry is highly competitive and new products and technologies evolve and come to market at a rapid pace.

The companies operating in this market include multinational organizations, established biotechnology companies, single product pharmaceutical and biotechnology companies, specialty pharmaceutical companies, and generic drug companies.

The companies operating in this market include multinational organizations,

established biotechnology companies, single product pharmaceutical and biotechnology companies, specialty pharmaceutical companies, and generic drug companies.

Many of the larger, established organizations currently have commercialization capabilities in-house, and may have partnership or license agreements in place with smaller companies for commercialization rights.

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The level of generic competition and the availability of reimbursement from government and other third-party payors will also significantly affect the pricing and competitiveness of our products.

We expect that, if approved by the FDA, Anaphylm would compete with several existing products and other product candidates that target Type I allergic reactions.

Among these are needle device-based treatments that have been accepted as standard of care treatment for many years, including autoinjectors such as EpiPen® marketed by Teva, and generics of EpiPen marketed by Viatris, Inc., Adrenaclick® marketed by Amneal Pharmaceuticals, LLC, and Auvi-Q® marketed by Kaleo Inc.

and syringe device Symjepi® marketed by US Worldmeds.

In August 2024, ARS Pharmaceuticals, Inc.

announced its product Neffy® , a nasal spray epinephrine delivery device, was approved by the FDA and EMA for the treatment of severe allergic reactions, including anaphylaxis.

Subsequently, ARS announced a licensing agreement with ALK-Abello A/S to commercialize Neffy in Europe, Canada and other territories outside of the United States.

Neffy is currently marketed and available to patients in the U.S.

There are other non-needle device based treatments in earlier phases of development that have not yet been approved for marketing in the United States by the FDA.

Anaphylm is the first and only orally delivered epinephrine product candidate in development to demonstrate clinical results comparable to autoinjectors such as EpiPen and Auvi-Q for the emergency treatment of allergic reactions, including anaphylaxis.

We believe Anaphylm is well positioned as a non-device based treatment option for this indication, if approved by the FDA, due to its comparable efficacy to existing auto-injector and nasal spray products, easy portability and convenience of use.

On January 10, 2020, a competitor of Aquestive obtained FDA approval of its diazepam nasal spray drug candidate, Valtoco, and was granted orphan-drug-exclusivity for this drug commencing as of January 10, 2020.

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This orphan drug exclusivity approval prevents a subsequent product seeking FDA approval from being marketed in the United States during the exclusivity period for the same active moiety for the same orphan drug indication except in the case where the drug candidate sponsor is able to demonstrate, and the FDA concludes, that the later drug is “clinically superior” to the approved products ( e.g.

, safer, more effective, or providing a

major contribution to patient care) within the meaning of FDA regulations and guidance.

, safer, more effective, or providing a major contribution to patient care) within the meaning of FDA regulations and guidance.

In assessing whether a drug candidate sponsor has demonstrated that its drug candidate provides a “major contribution to patient care” over and above the currently approved drugs, which is evaluated by the FDA on a case by case basis, there is no single objective standard and the FDA may, in appropriate circumstances, consider such factors as convenience of treatment location, duration of treatment, patient comfort, reduced treatment burden, advances in ease and comfort of drug administration, longer periods between doses, and potential for self-administration.

In August 2022, the FDA granted tentative approval for Libervant for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity ( i.e ., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.

The FDA concluded that Libervant has met all required quality, safety, and efficacy standards for approval.

Due to an existing FDA regulatory grant of orphan drug market exclusivity for our competitor’s diazepam nasal spray product discussed above, Libervant is not yet eligible for marketing in the United States.

As a result of the FDA determination, the FDA cannot give final approval for Libervant until the expiration of the orphan drug market exclusivity.

We continue to believe that, particularly in the case of our submitted studies on the effect of food on the absorption of diazepam formulations, Libervant has the distinct advantage of being able to be readily administered when needed without regard to food, providing an important benefit to patients.

In September 2023, the FDA accepted Aquestive's NDA for Libervant (diazepam) Buccal Film for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity ( i.e.

, seizure clusters, acute repetitive seizures) in patients between two and five years of age.

Diastat (diazepam) Rectal Gel is the only FDA approved treatment currently available to this patient population for this indication.

The NDA for Libervant was assigned a PDUFA target action date of April 28, 2024.

There is no assurance that, if the pediatric NDA for Libervant is approved by the FDA, it will overcome the orphan drug exclusivity granted by the FDA for Valtoco and be granted U.S.

market access for this patient age group.

Further, there can be no assurance that another company will not obtain other FDA market exclusivity that blocks U.S.

market access for Libervant for any age group in this patient population.

In August 2022, the FDA granted tentative approval for Libervant for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity ( i.e ., seizure clusters, acute repetitive seizures) (or ARS) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.

The FDA concluded that Libervant had met all required quality, safety, and efficacy standards for approval.

However, as a result of the orphan drug marketing exclusivity previously granted by the FDA to a nasal spray product, the FDA cannot give final approval for U.S.

market access for Libervant for any age group of 6 years and above until the expiration or inapplicability of the orphan drug market exclusivity scheduled to occur in January, 2027.

Due to this existing FDA regulatory grant of orphan drug market exclusivity, the FDA determined that Libervant was not yet eligible for marketing in the United States for this patient population of 12 years of age and older.

We expect to file for FDA approval of these epilepsy patients aged between 6 and 12 years prior to the expiration of the orphan drug marketing exclusivity block of the nasal spray product.

In September 2023, the FDA accepted Aquestive's NDA for Libervant (diazepam) Buccal Film for ARS patients between two and five years of age.

On April 26, 2024, the FDA approved Libervant for U.S.

market access for ARS patients between two and five years of age.

Libervant is the first and only orally administered rescue product for the treatment of ARS patients between ages two and five years.

The only other current FDA approved product on the market for these epilepsy patients between two and five years of age is a diazepam rectal gel.

On December 18, 2024 the FDA granted seven years of ODE to Libervant for the treatment of ARS patients between two and five years of age.

In October 2024, Libervant 5mg, 7.5mg, 10mg, 12.5mg and 15 mg for ARS patients between two and five years of age became available through multiple retail distribution channels.

Market access activities have broadened coverage.

Libervant is available nationwide with retail distribution capabilities in place.

For Medicaid patients, Libervant is available in all states.

Commercial patient access to Libervant continues to expand based on health plan reviews and Pharmacy Benefit Manager agreements.

On February 14, 2025, in a lawsuit brought by Neurelis, Inc.

("Neurelis") against the FDA ( Neurelis, Inc.

Califf, for which the Company joined as a Defendant Intervenor) challenging the FDA's approval of Libervant for ARS patients aged between two and five years, the U.S.

District for the District of Columbia issued a final appealable order entering a judgment in favor of Neurelis's motion for summary judgement and vacating the FDA’s approval of Libervant.

The District Court's ruling was not based on grounds of safety or efficacy of Libervant, but rather on the grounds that the law granting ODE to the FDA approved nasal spray for ARS patients aged six and older should be interpreted to extend to children aged two to five, despite that Valtoco was not approved by the FDA to treat these younger patients.

The Company is appealing this ruling and has filed a motion to stay the court's ruling pending the outcome of the appeal.

The Company is continuing to market and sell Libervant in the ordinary course, pending a final non-appealable ruling in this matter.

See Part II, Item 8.

Financial Statements and Supplementary Data, Note 23, Contingencies.

Material Agreements

More details regarding material agreements are described in Part IV Notes to Consolidated Financial Statements, Note 6, Material Agreements .

More details regarding material agreements are described in Part II, Item 8.

Financial Statements and Supplementary Data, Note 7, Material Agreements .

Intellectual Property

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Where our intellectual property is not protected by patents, we may seek to protect it through other means, including maintenance of trade secrets and careful protection of our proprietary information.

In addition, we intend to seek orphan drug exclusivity in jurisdictions in which it is available.

A prerequisite to orphan drug exclusivity in the United States and in the EU is orphan drug designation.

An orphan drug designation may be granted where a drug is developed specifically to treat a rare or uncommon medical condition.

If a product which has an orphan drug designation subsequently receives the first regulatory approval for the indication for which it has such designation, the product is entitled to orphan drug exclusivity, meaning that the applicable regulatory authority may not approve any other applications to market the same drug for the same indication, except in certain very limited circumstances, for a period of 7 years in the United States and 10 years in the EU.

Orphan drug exclusivity does not prevent competitors from developing or marketing different drugs for the indication protected by exclusivity, or the same drug for a different indication.

Our patent portfolio currently comprises at least 110 issued patents worldwide, of which at least 28 are U.S.

patents, and more than 150 pending patent applications worldwide.

These issued patents and pending patent applications provide both process of making and composition of matter protection for our PharmFilm technology and products and product candidates, including Suboxone and our PharmFilm formulations of tadalafil, diazepam, clobazam, riluzole, and epinephrine.

These issued patents and pending patent applications provide both process of making and composition of matter protection for our PharmFilm technology and products and product candidates, including Suboxone, Libervant and Anaphylm and our PharmFilm formulations of diazepam, clobazam, riluzole and epinephrine.

These patents and, if issued as patents, pending patent applications will likely expire between 2024 and 2044.

The pending patent applications filed in 2017 will provide composition of matter and process of making protection for our PharmFilm dosage formulations of diazepam and epinephrine and, if issued as patents, will likely expire by 2041.

The pending patent applications will provide composition of matter and process of making protection for our PharmFilm dosage formulations of diazepam and epinephrine and, if issued as patents, will likely expire by 2040 and 2044, respectively.

The projected expiration dates exclude any patent term adjustment or patent term extension.

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The patents and pending patent applications, if issued as patents, will likely expire between 2024 and 2044, excluding any patent term adjustment or patent term extension.

The PharmFilm technology patents and/or patent applications also generically and specifically protect the technology utilized in the products and product candidates in our CNS programs, our complex molecule programs, as well as our licensee programs.

The PharmFilm technology patents and/or patent applications also generically and specifically protect the technology utilized in the products in our CNS programs, our complex molecule programs, as well as our licensee programs.

For example, encompassed within our platform technology patents and/or patent applications is specific coverage directed to PharmFilm dosage formulations of CNS molecules such as diazepam.

Also encompassed within our platform technology is coverage for our complex molecule program which includes molecules such as epinephrine.

Our platform technology patents and/or patent applications further cover the products Suboxone and Zuplenz, as well as our formulations of the molecules apomorphine and tadalafil, which are part of our licensed programs.

The expiration dates for patents covering these products and product candidates, and for pending applications if issued as patents, extend from 2024 to 2041, excluding any patent term adjustment or patent term extension.

Also encompassed within our platform technology is coverage for our complex molecule program which includes molecules such as epinephrine and technology applicable to our product candidate Anaphylm.

Our platform technology patents and/or patent applications further cover the products Libervant, Suboxone and Ondif, as well as our formulations of the molecules apomorphine, which is part of our licensed programs.

The expiration dates for patents covering PharmFilm products and product candidates, and for pending applications if issued as patents, extend from 2024 to 2044, excluding any patent term adjustment or patent term extension.

We note that several of our issued patents are or have been involved in administrative proceedings, such as reexamination and inter partes review at the U.S.

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In the United States, pharmaceutical products are subject to extensive regulation by the FDA.

The Federal Food, Drug, and Cosmetic Act, or FDCA and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products.

The FDCA and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products.

Failure to comply with applicable FDA or other requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending applications, clinical holds, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, withdrawal of product from the market, injunctions, fines, civil penalties and criminal prosecution.

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• satisfactory completion of an FDA pre-approval inspection of the facility or facilities at which the product is manufactured to assess compliance with the FDA’s current cGMP regulations to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

• satisfactory completion of a potential review by an FDA advisory committee, if applicable;

• satisfactory completion of a potential review at a public FDA Advisory Committee meeting;

which is a meeting of independent outside experts that provide advice and recommendations to the FDA;

• FDA review and approval of the NDA.

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FDA approval of the NDA is required before marketing of the product may begin in the United States.

The NDA must include the results of all

preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls.

The NDA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls.

Under federal law, the submission of most NDAs is subject to a substantial application user fee, and applicant under an approved NDA is also subject to an annual program fee for each prescription drug product, which beginning in Fiscal Year 2018 replaced the product and establishment fees.

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Once the submission is accepted for filing, the FDA begins an in-depth substantive review.

Under PDUFA, the FDA has agreed to certain performance goals in the review of NDAs through a two-tiered classification system, Standard Review and Priority Review.

Under PDUFA, the FDA has agreed to certain performance goals in the review of NDAs through a two-tiered classification

system, Standard Review and Priority Review.

Priority Review designation is given to drugs that offer major advances in treatment or provide a treatment where no adequate therapy exists.

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Drug manufacturers and certain of their subcontractors are required to register their establishments with FDA and obtain licenses from certain state agencies.

Registration with the FDA subjects entities to periodic unannounced inspections by FDA, during which the agency inspects manufacturing facilities to assess compliance with cGMPs

or other applicable laws, such as adverse event recordkeeping and reporting.

Registration with the FDA subjects entities to periodic unannounced inspections by FDA, during which the agency inspects manufacturing facilities to assess compliance with cGMPs or other applicable laws, such as adverse event recordkeeping and reporting.

Accordingly, manufacturers must continue to expend time, money, and training and compliance efforts in the areas of production and quality control to maintain compliance with cGMPs or other applicable laws, such as adverse event recordkeeping and reporting requirements.

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In addition, other regulatory action, including, among other things, warning letters, the seizure of products, injunctions, consent decrees placing significant restrictions on or suspending manufacturing operations, civil penalties, and criminal prosecution may be pursued.

In addition, any distribution of prescription drug products must comply with the U.S.

Prescription Drug Marketing Act, or PDMA, a part of the FDCA.

In addition, Title II of the Federal Drug Quality and Security Act of 2013, known as the DSCSA has imposed new “track and trace” requirements on the distribution of prescription drug products by manufacturers, distributors, and other entities in the drug supply chain.

In addition, any distribution of prescription drug products must comply with the PDMA, a part of the FDCA.

In addition, Title II of the Federal Drug Quality and Security Act of 2013, known as the DSCSA has imposed new “track and

trace” requirements on the distribution of prescription drug products by manufacturers, distributors, and other entities in the drug supply chain.

These requirements are being phased in over a ten-year period.

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This last certification is known as a paragraph IV certification.

A notice of the paragraph IV certification must be provided to each owner of the

patent that is the subject of the certification and to the holder of the approved NDA to which the ANDA or 505(b)(2) application refers.

A notice of the paragraph IV certification must be provided to each owner of the patent that is the subject of the certification and to the holder of the approved NDA to which the ANDA or 505(b)(2) application refers.

The applicant may also elect to submit a “section viii” statement certifying that its proposed label does not contain (or carves out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent.

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In addition, HIPAA, and its implementing regulations impose certain obligations on entities subject to the law, such as health plans and most healthcare providers, and their business associates who provide certain services involving the use or disclosure of HIPAA protected health information on their behalf, with respect to the privacy and security of such protected health information.

Further, most states have enacted laws governing the privacy and security of health information in certain

circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts in certain circumstances, such as specific disease states.

Further, most states have enacted laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts in certain circumstances, such as specific disease states.

Compliance with such laws and regulations requires substantial resources.

While we no longer engage in the commercial sale of any proprietary drug products, we may engage in the commercial sale of proprietary products in the future.

In addition, because of the breadth of these various fraud and abuse laws, it is possible that some of our business activities in the past could be subject to challenge under one or more of such laws.

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In the event governmental authorities conclude that our business practices did not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations, they may impose sanctions under these laws, which are potentially significant and may include civil monetary penalties, damages, exclusion of an entity or individual from participation in government health care programs, criminal fines and individual imprisonment, additional reporting requirements if we become subject to a corporate integrity agreement or other settlement to resolve allegations of violations of these laws, as well as the potential curtailment or restructuring of our operations.

Further, we may be subject to contractual damages and reputational harm as result of such non-compliance.

Further, we may be

subject to contractual damages and reputational harm as result of such non-compliance.

Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity.

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The European Medicines Agency, or EMA, implemented the centralized procedure for the approval of human medicines to facilitate marketing authorizations that are valid throughout the EU.

This procedure results in a single marketing authorization issued by the European Commission following a favorable opinion by the EMA that is valid across the European Union, as well as Iceland, Liechtenstein and Norway.

This procedure results in a single marketing authorization issued by the European Commission following a favorable opinion by the EMA that is valid across the EU, as well as Iceland, Liechtenstein and Norway.

The centralized procedure is compulsory for human medicines that are:

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National authorization procedures .

There are also two other possible routes to authorize medicinal products in several European Union countries, which are available for investigational medicinal products that fall outside the scope of the centralized procedure:

There are also two other possible routes to authorize medicinal products in several EU countries, which are available for investigational medicinal products that fall outside the scope of the centralized procedure:

the decentralized procedure and the mutual recognition procedure.

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In the United States, PPACA substantially changed the way healthcare is financed by both governmental and private insurers and significantly impacted the pharmaceutical industry.

Changes that may affect our business include those governing enrollment in federal healthcare programs, reimbursement changes, benefits for patients within a coverage gap in the Medicare Part D prescription drug program, or commonly known as the donut hole in which manufacturers must agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, rules regarding prescription drug benefits under the health insurance exchanges, changes to the Medicaid Drug Rebate program, expansion of the Public Health Service’s 340B drug pricing discount program, or 340B program, fraud and abuse, and enforcement.

Changes that may affect our business include those governing enrollment in federal healthcare programs, reimbursement changes, benefits for patients who have reached the “catastrophic coverage” out-of-pocket limit under the Medicare Part D prescription drug program, rules regarding prescription drug benefits under the health insurance exchanges, changes to the Medicaid Drug Rebate program, expansion of the Public Health Service’s 340B drug pricing discount program, or 340B program, fraud and abuse, and enforcement.

These changes impacted existing government healthcare programs and are resulting in the development of new programs, including Medicare payment for performance initiatives and improvements to the physician quality reporting system and feedback program.

Some states have elected not to expand their Medicaid programs to individuals with an income of up to 133% of the federal poverty level, as is permitted under the PPACA.

For each state that does not choose to expand its Medicaid program, there may be fewer insured patients overall, which could impact our sales of products for which we receive regulatory approval, business and financial condition.

For each state that does not choose to expand its Medicaid program,

there may be fewer insured patients overall, which could impact our sales of products for which we receive regulatory approval, business and financial condition.

Where new patients receive insurance coverage under any of the new Medicaid options made available through the PPACA, the possibility exists that manufacturers may be required to pay Medicaid rebates on drugs used under these circumstances, a decision that could impact manufacturer revenues.

Since its enactment, there have been numerous judicial, administrative, executive, and legislative challenges to certain aspects of the PPACA, and we expect there will be additional challenges and amendments to the PPACA in the future.

Various portions of the PPACA are currently undergoing legal and constitutional challenges in the United States Supreme Court, previous administrations issued various Executive Orders which eliminated cost-sharing subsidies and various provisions that would impose a fiscal burden on states or a cost, fee, tax, penalty or regulatory burden on individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices;

and Congress has introduced several pieces of legislation aimed at significantly revising or repealing the PPACA.

While the United States Supreme Court has generally upheld the constitutionality of the PPACA, cases challenging its legal and constitutional validity continue to be heard by the Supreme Court.

Executive Orders have been issued and repealed by successive presidential Administrations, making it uncertain what fiscal burdens might be placed on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices at any given time.

In each session of Congress, bills have been introduced that might significantly expand, revise or repeal the PPACA.

It is unclear whether the PPACA will be overturned, repealed, replaced, or further amended.

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Such scrutiny has resulted in several recent Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

On July 24, 2020, four Executive Orders were signed and enacted directing the Secretary of HHS to:

(1) eliminate protection under an Anti-Kickback Statute safe harbor for certain retrospective price reductions provided by drug manufacturers to sponsors of Medicare Part D plans or pharmacy benefit managers that are not applied at the point-of-sale, which may be delayed until 2032 by the recent Consolidated Appropriations Act ;

(2) allow the importation of certain drugs from other countries through individual waivers, permit the re-importation of insulin products, and prioritize finalization of FDA’s December 2019 proposed rule to permit the importation of drugs from Canada;

(3) ensure that payment by the Medicare program for certain Medicare Part B drugs is not higher than the payment by other comparable countries (depending on whether pharmaceutical manufacturers agree to other measures);

and (4) allow certain low-income individuals receiving insulin and epinephrine purchased by a FQHC, as part of the 340B drug program to purchase those drugs at the discounted price paid by the FQHC.

On October 1, 2020, the FDA issued its final rule allowing importation of certain prescription drugs from Canada.

On September 13, 2020, President Trump signed an Executive Order directing HHS to implement a rulemaking plan to test a payment model, pursuant to which Medicare would pay, for certain high-cost prescription drugs and biological products covered by Medicare Part B, no more than the most-favored-nation price (i.e., the lowest price) after adjustments, for a pharmaceutical product that the drug manufacturer sells in a member country of the Organization for Economic Cooperation and Development that has a comparable per-capita gross domestic product.

While some proposed measures will require authorization through additional legislation to become effective, Congress has indicated that they will continue to pursue new legislative and/or administrative measures to control drug costs, including price or patient reimbursement constraints, discounts, restrictions on certain access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Most recently, the Inflation Reduction Act of 2022, or IRA, included a number of significant drug pricing reforms, which include the establishment of a drug price negotiation program within the HHS (beginning in 2026) that requires manufacturers to charge a negotiated “maximum fair price” for certain selected drugs or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers under Medicare Parts B and D to penalize price increases that outpace inflation (first due in 2023), and a redesign of the Part D benefit, as part of which manufacturers are required to provide discounts on Part D drugs (beginning in 2025).

It is difficult at this time to predict whether additional executive or legislative initiatives may be proposed related to drug pricing.

For example, the Inflation Reduction Act of 2022 (“IRA”), signed into law by President Biden, included a number of significant drug pricing reforms, which include the establishment of a drug price negotiation program within the HHS (beginning in 2026) that requires manufacturers to charge a negotiated “maximum fair price” for certain selected drugs or pay an excise tax for noncompliance, the establishment of rebate payment requirements on manufacturers under Medicare Parts B and D to penalize price increases that outpace inflation, and a redesign of the Part D benefit, a part of which requires manufacturers to provide discounts on Part D drugs starting in 2025.

Congress has further indicated that they will continue to pursue new legislative and/or administrative measures to control drug costs, including price or patient reimbursement constraints, discounts, restrictions on certain access and marketing cost disclosure and transparency measures, and, in some cases, laws designed to encourage importation from other countries and bulk purchasing.

Each recent presidential administration has enacted and repealed Executive Orders that have impacted prescription drug prices.

In his first term, President Trump enacted Executive Orders directing the Secretary of HHS to eliminate protection under an Anti-Kickback Statute safe harbor for certain retrospective price reductions, ensure that payment by the Medicare program for certain Medicare Part B drugs is not higher than the payment by other comparable countries, allow certain low-income individuals purchase insulin and epinephrine, and implement a rulemaking plan to test a payment model, pursuant to which Medicare would receive most-favored-nation prices ( i.e ., the lowest price) for certain pharmaceutical products.

President Biden enacted Executive Orders to, among other things, reduce barriers to the PPACA marketplace, increase the affordability of the marketplace and increase eligibility for and coverage from the marketplace and Medicaid.

On the first day of President Trump’s second term, he revoked many of President Biden’s Executive Orders, including such Orders impacting Medicaid and the PPACA.

It is difficult at this time to predict what future executive or legislative initiatives may impact drug pricing.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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As discussed above, the cost of pharmaceuticals continues to generate substantial governmental and third‑party payor interest.

We expect that the pharmaceutical industry will experience pricing pressures, given the trend toward managed healthcare, the increasing influence of managed care organizations, and additional regulatory and legislative proposals.

We expect that the pharmaceutical industry will continue to experience pricing pressures, given the trend toward managed healthcare, the increasing influence of managed care organizations, and additional regulatory and legislative proposals.

Our results of operations and business could be adversely affected by current and future third‑party payor policies, as well as healthcare legislative reforms.

Additionally, discounted pricing or rebates on purchases of pharmaceutical products must be offered under various federal and state healthcare programs, including:

the Centers for Medicare & Medicaid Services’ Medicaid Drug Rebate Program, Medicare Part B Program and Medicare Part D Coverage Gap Discount Programs, the U.S.

the Centers for Medicare & Medicaid Services’ Medicaid Drug Rebate

Program, Medicare Part B Program and Medicare Part D Manufacturer Discount Programs, the U.S.

Department of Veterans Affairs’ Federal Supply Schedule Program, and the Health Resources and Services Administration’s 340B Drug Pricing Program.

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We provide ongoing training in support of that commitment.

We remain proactive in ensuring the safety of our colleagues, their families, our patients and our products as we continue to monitor the COVID-19 landscape both in the United States and globally.

We were able to overcome many of the challenges presented by the worldwide COVID-19 pandemic by engaging colleagues early and often through organizational messaging aimed at reinforcing our commitment to safety.

We continue to engage and educate our colleagues to prevent the spread of COVID-19 to minimize any impact to our business.

We follow the CDC guidelines and provide testing to and quarantining of colleagues, when necessary.

Environmental Safety

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Our annual, quarterly, periodic and current reports, proxy statements and other public filings are also available free of charge on the EDGAR Database on the SEC’s Internet website at www.sec.gov.

Business Update Regarding COVID-19

The extent to which COVID-19 impacts our business, operations, clinical trials, regulatory approval process, capital, financial and monetization markets, financial results and financial condition, and those of our suppliers, distributors, customers and other third parties necessary to our business including those involved in the regulatory approval process, will depend on future developments, which are highly uncertain and cannot be predicted with certainty or clarity, including the duration and continuing severity of the outbreak, resurgence of the outbreak, continued or additional government actions to contain COVID-19, efficacy of vaccines, and new information that will emerge concerning the short-term and long-term impact of COVID-19.

To date, we have been able to continue to manufacture and supply our products and currently do not anticipate any significant interruption in supply, although we continue to monitor this situation closely and there is no assurance that disruptions or delay will not occur as a result of COVID-19.

We are also monitoring demand for our products, which could be negatively impacted during the COVID-19 pandemic, as well as the financial condition of our customers and licensees.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business