Aquestive Therapeutics, Inc 8-K, filed Mar 25, 2021
Aquestive Therapeutics, Inc. (AQST)
8-K
2021-03-25
For: 2021-03-25
View Original
Added on
April 09, 2026
About this 8-K
Aquestive Therapeutics, Inc filed this 8-K on March 25, 2021.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 8.01: Other events
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported): March 25, 2021
Aquestive Therapeutics, Inc.
(Exact name of Registrant as specified in its charter)
|
Delaware
|
001-38599
|
82-3827296
|
|
(State or Other Jurisdiction of Incorporation or Organization)
|
(Commission File Number)
|
(I.R.S. Employer Identification No.)
|
30 Technology Drive
Warren, NJ 07059
(908) 941-1900
(Address, Including Zip Code, and Telephone Number, Including Area Code, of Registrant’s Principal Executive Offices)
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ |
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
|
| ☐ |
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
|
| ☐ |
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
|
| ☐ |
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
|
Securities registered pursuant to Section 12(b) of the Act:
|
Title of each class
|
Trading Symbol(s)
|
Name of each exchange on which registered
|
|
Common Stock, par value $0.001 per share
|
AQST
|
Nasdaq Global Market
|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange
Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards
provided pursuant to Section 13(a) of the Exchange Act. ☐
|
Item 7.01
|
Regulation FD Disclosure.
|
Aquestive Therapeutics, Inc. (the “Company”) is furnishing this Current Report on Form 8-K in connection with the disclosure of information, in the form of an investor presentation, to
be given at meetings with institutional investors, analysts and others (the “R&D Event”). This information may be amended or updated at any time and from time to time through another Current Report on Form 8-K, a later company filing or
other means. A copy of the Company’s investor presentation is attached hereto as Exhibit 99.1 to this Current Report on Form 8-K and incorporated into this Item 7.01 by reference and replaces in its entirety all prior investor presentations
filed by the Company. The investor presentation is available on the Company’s website located at www.aquestive.com, although the Company reserves the right to discontinue that availability at any
time.
The information in this Item 7.01 (including Exhibit 99.1) shall not be deemed to be “filed” for purposes of, or otherwise subject to the liabilities of, Section 18 of the Securities Exchange Act of
1934, as amended (the “Exchange Act”), nor shall it be deemed to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in any
such filing.
| Item 8.01 |
Other Events.
|
On March 25, 2021, the Company issued a press release providing a business update in connection with the R&D Event being hosted by the Company. A copy of the Company’s press release is attached
hereto as Exhibit 99.2 and incorporated into this Item 8.01 by reference.
|
Item 9.01
|
Financial Statements and Exhibits
|
| (d) |
Exhibits.
|
|
Exhibit Number
|
Description
|
|
|
Investor presentation.
|
||
|
Press Release dated March 25, 2021.
|
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
Dated: March 25, 2021
|
Aquestive Therapeutics, Inc.
|
|
|
By:
|
/s/ A. Ernest Toth, Jr.
|
|
|
Name: A. Ernest Toth, Jr.
|
||
|
Title: Interim Chief Financial Officer
|
||
Exhibit 99.1
Anaphylaxis and EpinephrineR&D Day March 25, 2021
Forward Looking Statement This presentation includes forward-looking statements within the meaning of
the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “anticipate,” “plan,” “expect,” “estimate,” “intend,” “may,” “will,” or the negative of those terms, and similar expressions, are intended to identify
forward-looking statements. These forward-looking statements include, but are not limited to, statements regarding the advancement of Libervant, AQST-108, AQST-109 and other product candidates through the regulatory and development pipeline;
and business strategies, market opportunities, and other statements that are not historical facts. These forward-looking statements are subject to the uncertain impact of the COVID-19 global pandemic on our business including with respect to
our clinical trials including site initiation, patient enrollment and timing and adequacy of clinical trials; on regulatory submissions and regulatory reviews and approvals of our product candidates; pharmaceutical ingredient and other raw
materials supply chain, manufacture, and distribution; sale of and demand for our products; our liquidity and availability of capital resources; customer demand for our products and services; customers’ ability to pay for goods and services;
and ongoing availability of an appropriate labor force and skilled professionals. Given these uncertainties, the Company is unable to provide assurance that operations can be maintained as planned prior to the COVID-19 pandemic.These
forward-looking statements are based on our current expectations and beliefs and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.
Such risks and uncertainties include, but are not limited to, risks associated with the Company's development work, including any delays or changes to the timing, cost and success of our product development activities and clinical trials and
plans for AQST-108, AQST-109 and our other drug candidates; risk of delays in FDA approval of our drug candidates, Libervant and AQST-108, AQST-109, and our other drug candidates or failure to receive approval; ability to address the concerns
identified in the FDA’s Complete Response Letter dated September 25, 2020 regarding the New Drug Application for Libervant; risk of our ability to demonstrate to the FDA “clinical superiority” within the meaning of the FDA regulations of
Libervant relative to FDA-approved diazepam rectal gel and nasal spray products including by establishing a major contribution to patient care within the meaning of FDA regulations relative to the approved products as well as risks related to
other potential pathways or positions which are or may in the future be advanced to the FDA to overcome the seven year orphan drug exclusivity granted by the FDA for the approved nasal spray product of a competitor in the U.S. and there can be
no assurance that we will be successful; risk that a competitor obtains FDA orphan drug exclusivity for a product with the same active moiety as any of our other drug products for which we are seeking FDA approval and that such earlier approved
competitor orphan drug blocks such other product candidates in the U.S. for seven years for the same indication; risk inherent in commercializing a new product (including technology risks, financial risks, market risks and implementation risks
and regulatory limitations); risk of development of our sales and marketing capabilities; risk of legal costs associated with and the outcome of our patent litigation challenging third party at risk generic sale of our proprietary products;
risk of sufficient capital and cash resources, including access to available debt and equity financing and revenues from operations, to satisfy all of our short-term and longer term cash requirements and other cash needs, at the times and in
the amounts needed; risk of failure to satisfy all financial and other debt covenants and of any default; our and our competitors’ orphan drug approval and resulting drug exclusivity for our products or products of our competitors; short-term
and long-term liquidity and cash requirements, cash funding and cash burn; risk related to government claims against Indivior for which we license, manufacture and sell Suboxone® and which accounts for the substantial part of our current
operating revenues; risks related to the outsourcing of certain marketing and other operational and staff functions to third parties; risk of the rate and degree of market acceptance of our product and product candidates; the success of any
competing products, including generics; risk of the size and growth of our product markets; risks of compliance with all FDA and other governmental and customer requirements for our manufacturing facilities; risks associated with intellectual
property rights and infringement claims relating to the Company's products; risk of unexpected patent developments; the impact of existing and future legislation and regulatory provisions on product exclusivity; legislation or regulatory
actions affecting pharmaceutical product pricing, reimbursement or access; claims and risks that may arise regarding the safety or efficacy of the Company's products and product candidates; risk of loss of significant customers; risks related
to legal proceedings, including patent infringement, investigative and antitrust litigation matters; changes in government laws and regulations; risk of product recalls and withdrawals; uncertainties related to general economic, political,
business, industry, regulatory and market conditions and other unusual items; and other uncertainties affecting the Company described in the “Risk Factors” section and in other sections included in our Annual Report on Form 10 K, in our
Quarterly Reports on Form 10-Q, and in our Current Reports on Form 8-K filed with the Securities Exchange Commission (SEC). Given those uncertainties, you should not place undue reliance on these forward-looking statements, which speak only as
of the date made. All subsequent forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. The Company assumes no obligation to update
forward-looking statements or outlook or guidance after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by applicable law.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.This presentation shall not constitute an offer to sell or the solicitation of an offer to buy
these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or
jurisdiction.
Today’s Agenda Topic Presenter(s) Introductions Keith Kendall, CEODan Barber, COO Medical Overview
of Anaphylaxis and Epinephrine David M. Fleischer, MD, FAAAAIProfessor of Pediatrics, Section Head, Allergy and Immunology, Children’s Hospital ColoradoUniversity of Colorado Denver School of Medicine Anaphylaxis Market Overview Michael
Arcara, MBA Commercial Lead, Allergy R&D Overview of AQST-108 and AQST-109 Steve Wargacki, PhDVP of R&D, Aquestive Therapeutics Clinical Lessons from Today’s Products John Oppenheimer, MD Clinical Professor of Medicine at UMDNJ
Rutgers, Pulmonary and Allergy Associates NJ Clinical Overview of AQST-108 and AQST-109 Mark Lepore, MD Chief Medical Officer, Allergy, Aquestive Therapeutics Q&A Closing Remarks Keith Kendall, CEO ®
PharmFilm® Technology – Where You Need It, When You Need It™ And Needle Free
David M. Fleischer, MD, FAAAAIProfessor of PediatricsSection Head, Allergy and ImmunologyChildren’s
Hospital ColoradoUniversity of Colorado Denver School of Medicine Anaphylaxis and EpinephrineMedical Overview
Introduction David M. Fleischer, MD, FAAAAIProfessor of PediatricsSection Head, Allergy and
ImmunologyChildren’s Hospital ColoradoUniversity of Colorado Denver School of Medicine
Defining Anaphylaxis Simons FE. J Allergy Clin Immunol. 2009;124(4):625-636. Patients
at risk for anaphylaxis should have a long-term allergy-management plan Poses serious consequences for at-risk patients Often occurs in the community setting Anaphylaxis is a severe systemic allergic reaction that is rapid in onset and can
cause death
Common Triggers of Anaphylaxis Idiopathic anaphylaxis Exercise Insect venom, medications, and
latex
Common Signs and Symptoms of Anaphylaxis *Potentially life-threatening symptoms. Simons FE. J
Allergy Clin Immunol. 2009;124(4):625-636. Central nervous system10%-15% of episodesUneasiness, throbbing headache, dizziness, confusion, tunnel vision Airway*70% of episodesLarynx: pruritus and tightness in throat; dysphonia and
hoarsenessLung: dyspnea, chest tightness, wheezing/bronchospasm Skin 80%-90% of episodesUrticaria, pruritus, flushingMucosal tissue: pruritus and swelling of lips, tongue, uvula/palate Cardiovascular system*10%-45% of episodesChest pain,
hypotension, tachycardia, weak pulse, dizziness, fainting Gastrointestinal tract30%-45% of episodesNausea, cramping, abdominalpain, vomiting, diarrhea
Patterns of Anaphylaxis UniphasicSigns and symptoms within minutes of exposure to an offending
stimulusBiphasicBiphasic anaphylaxis has an immediate phase with a period of improvement and response to initial therapy, but with recurrent symptoms 2 to 6 hours after the onset of the initial reactionProtractedProtracted anaphylaxis causes
prolonged manifestations (usually respiratory distress or hypotensive shock) for 5 to 32 hours Golden D. Novartis Found Symp. 2004;257:101-110. Anaphylaxissigns and symptoms (minutes to hours) Signs and symptomsoccur 2 to 6 hours
after initial reaction Allergenexposure Likelihood of Occurrence Initial reaction Biphasic reaction 5 m 10 m 15 m 20 m 25 m 30 m 1 h 8 h 72h 2 h 3 h 4 h 5 h 6 h 7 h 9 h 10 h
Epinephrine is first-line treatment for anaphylaxis1Fatality due to anaphylaxis is associated with
delayed epinephrine administration2Failure to administer epinephrine in a timely manner (eg, pre-ED) has been associated with fatalities3Failure to administer epinephrine promptly is the most important factor contributing to death ED,
emergency department.1. Waserman S et al. J Allergy Clin Immunol Pract. 2017;5:1180-1191; 2. Song TT, Lieberman P. Curr Opin Allergy Clin Immunol. 2015;15(4):323-328; 3. Simons FE et al. J Allergy Clin Immunol.
1998;101:33-37. Epinephrine Allergy suspected in mother’s death
Use and Carry Practices for Epinephrine Auto-Injectors Correct use of epinephrine auto-injectors (EAIs)
is surprisingly lowData indicate just 16% to 32%1Studies have shown that:Just half of at-risk patients regularly carry an unexpired EAI2Many patients did not have epinephrine available at the time of a reaction3A majority of caregivers did not
give their allergic children epinephrine at the time of their most severe allergic reactions4 1. 1. Bonds RS et al. Misuse of medical devices. Ann Allergy Asthma Immunol. 2015;114(1):74e76.e2; 2. Arkwright PD, Farragher AJ. Pediatr Allergy
Immunol. 2006;17(3):227e229; 3. Polloni L et al. Pediatr Allergy Immunol. 2020;31(4):380e387; 4. Egan M et al. J Allergy Clin Immunol Pract. 2019;7(2):655e658; 5. Warren CM et al. Ann Allergy Asthma Immunol. 2018;121(4):479e489.e2.. Images:
EpiPen Package Insert, Patient Directions for Use Most common reasons for pitfalls in the use of EAIs are:Lack of auto-injector availabilityInadequate education on how to administer the epinephrineConcern for systemic effects, failure to
administer correctly, and accidental administration5
Adverse Events Due to Incorrect Use of EAIs Publications have raised concerns over laceration and
embedded-needle injuries resulting from the use of EAIs1From 1994 to 2007, >15,000 unintentional injections from EAIs were reported to US Poison Control CentersThose unintentionally injected had a median age of 14 years2Even if EAIs are
available, safety concerns and/or fear of needles may prevent them from being administered in a timely manner1 1. Posner L, Camargo CA Jr. Drug Healthc Patient Saf. 2017;9:9-18; 2. Simons FER et al. J Allergy Clin Immunol.
2010;125(2):419-423.e4. 3. Image: Brown J et al. Lacerations and Embedded Needles Caused by EEAI Use in Children. Annals of Emergency Medicine, 2015.
EAI Refill Rates Are Suboptimal Lack of annual EAI refills can leave at-risk patients without immediate
access to epinephrine when they need itIn 1 large HMO over a 5-year period:A total of just 46% of patients refilled their EAI at least once Just 25% refilled multiple timesOnly 11% refilled each year Kaplan. Curr Allergy Asthma Rep.
2011;11:65-70.
Summary Anaphylaxis is an unpredictable, severe systemic allergic reaction that is rapid in onset and
potentially fatalAt-risk patients should always have immediate access to 2 doses of epinephrineFatality due to anaphylaxis is associated with delayed epinephrine administrationFar too few at-risk patients:Carry their EAI with themRefill their
EAI on an ongoing basisAre confident, timely, and accurate in their use of an EAI during an emergency situationEpinephrine products that are easier for patients to carry and administer would be an important addition to an allergist’s treatment
armamentarium
Michael Arcara Anaphylaxis and EpinephrineMarket Overview
Introduction Michael ArcaraCommercial Lead, AllergyMBA, University of Michigan25 years experience in
pharmaceutical commercial developmentEpinephrine-specific experience: Mylan (EpiPen); Valeant (Emerade)
Epidemiology: Life-Threatening Allergic Reaction1,2 Anaphylaxis epidemiology is not well definedStudies
estimate that 1.6% to 5.1% of the US population has actually had an anaphylaxis episodeOne set of data indicates that people dying from food allergy often had previous reactions but these were typically not severe3Per CDC: the prevalence of
food allergies in children increased by 50% between 1997 and 2011 1. Woods et al. J Allergy Clin Immunol. 2014;133:461-467; 2. Food Allergy Research & Education website. https://www.foodallergy.org/resources/facts-and-statistics; 3.
Pumphrey R. Anaphylaxis: can we tell who is at risk of a fatal reaction? Curr Opin Allergy Immunol. 2004.
Overview: Epinephrine Market Prescription market was still growing and peaked just before Teva generic
entered2018-current = significantly diminished HCP/consumer promotionLarge percentage of EAI prescriptions—especially first-time prescriptions—are driven by allergists and pediatriciansTarget HCP universe ~20,000 physiciansCurrent EpiPen ®
2-Pak WAC: ~$300 Epinephrine: US market 2014 2015 2016 2017 2018 2019 2020 Market prescriptions, millions 3.6 3.8 3.8 3.6 3.1 3.2 3.0 Market $, billions 1.4 1.9 2.4 2.1 1.8 1.9 1.5 Source: Symphony Health PHAST
(Pharmaceutical Audit Suite)
Physician Research: Providers Indicate Preference for Alternative Route of Administration 89% at least
somewhat prefer *Aquestive sponsored online survey; N=500 allergists, pediatricians, and PCPs; fielded 2018. Data on file. To what extent would you prefer an alternative administration route for epinephrine?
How concerned are you with patients and/or their caregivers consistently having their auto-injector(s)
with them when they leave home? Physician Research: Concerns About Patients Having EAI With Them at All Times 88% at least somewhat concerned *Aquestive sponsored online survey; N=500 allergists, pediatricians, and PCPs; fielded 2018. Data
on file.
Patient Survey: Unprompted Unmet Need Top 3 Box: 74% Top 4 Box: 88% *Aquestive sponsored online,
5-minute survey; N=75 EAI patients, 75 caregivers; fielded February 2021. Data on file To what extent would you prefer a new way to dose epinephrine?
Interest in the film medicine being available to replace your EAI Patient Survey: First Exposure to
Film Dosing At Least Some Interest: 99% *Aquestive sponsored online, 5-minute survey; N=75 EAI patients, 75 caregivers; fielded February 2021. Data on file
Patient Survey: Impact, Epinephrine On Hand I believe the smaller package would make it more likely for
me to have the film with me when I need it (vs EAI): *Aquestive sponsored online, 5-minute survey; N=75 EAI patients, 75 caregivers; fielded February 2021. Data on file
Patient Survey: Ask Doctor About Film Top 3 Box: 90% Top 4 Box: 96% How likely would you be to ask
your doctor about the film? *Aquestive sponsored online, 5-minute survey; N=75 EAI patients, 75 caregivers; fielded February 2021. Data on file
PharmFilm delivers market share within existing market Aquestive allergy franchise delivers
market expansion Our View of the Epinephrine Commercial Opportunity Features/benefits customers are looking for in a new epinephrine delivery:PortabilityUsabilityNeedle freeTemperature tolerability*Waterproof/resistant* Expected
opportunities to increase the customer base:Previously reluctant (e.g., needle-phobic or size-resistant) patients more readily adopt PharmFilm dosingIncreased carry rates due to size, in turn, increase engagement with the brand and annual
refill ratesGiven current lack of promotion in the market, Aquestive launch plans to re-engage HCPs, patients, and advocacy groups Patient convenience Medical advance + *Target Product Profile
Aquestive PharmFilm – Potential Annual Peak Net Sales* No market expansionPharmFilm share
<30% $500M $250M Modest market expansionPharmFilm share = 30% - 50% Significant market expansionPharmFilm share >50% *Potential sales revenues are based on current sales information from Symphony Health PHAST (Pharmaceutical Audit
Suite) (See Slide 19) assuming peak sales at ~5 years post launch.
Summary: Anaphylaxis and Epinephrine A large and growing patient population at risk for anaphylaxis
existsPharmFilm, as a dosage form, has the potential to deliver on physician- and patient-articulated unmet needs in the marketplace: smaller size and needle freeAquestive’s PharmFilm technology represents an exciting and significant pipeline
opportunity
Stephen Wargacki, Ph.D.Vice President R&D Anaphylaxis and EpinephrineAquestive Epinephrine Program
Introduction Stephen Wargacki, PhDVice President, R&DJoined Aquestive in 2015PhD, Polymer
ChemistryUniversity of TennesseePostdoctoral FellowAir Force Research Laboratory12 years experience in alternative drug delivery24 publications (286 citations)47 patents (18 patent families)
Challenges of Epinephrine for Anaphylaxis EPINEPHRINE ↑ CardiacOutput Dilates
Coronary Vessels ↑ Muscle Contraction Efficiency ↑ Fatty AcidRelease ↑ Mental Alertness ↑ ACTH & TSH Release ↑ Glycogen→Glucose ↓ Intestinal Mobility VARIABLE
Noninvasive Delivery of Epinephrine Why has science not overcome the challenges of alternative
epinephrine delivery? Overcome with Traditional Formulation Techniques Prevents rapid, consistent absorption Vasoconstriction Normal blood flow Restricted blood flow Hydrophilic Absorptionand Speed Unstable
PharmFilm® for Delivery of Oral Epinephrine Mean profiles for initial epinephrine film compared with
EpiPen® in Study 160455 EpiPen® 0.3mg (mean/SD) Epinephrine Sublingual Film (mean/SD) Time (minutes) Epinephrine plasma concentration [pg/mL]
Uses of Prodrugs in Pharmaceuticals * Since 2015, prodrugs have accounted for ~10% of all small
molecules that have come to market in the United States. Reference: European Journal of Pharmaceutical Sciences, (109) 2017, pg 146 What are prodrugs*? Drug with suboptimal properties Drug bounded to another molecule for improved
properties Drug released by metabolic processes
AQST-108: L-Dipivefrin Receptors Epinephrine (µM) Dipivefrin(µM) Dipivefrin vs Epi(ratio) α1
receptors 0.00018 0.41 2278 Property Epinephrine Dipivefrin Log P -0.43 3.71
Impact of AQST-108 on Sublingual Delivery of Epinephrine Increased absorption at similar dosesComparable
Cmax, AUC to injectable from previous study AQST-108 (N=6) Average Epinephrine Plasma Profile From Prototypes Generations 1 and 2 EpiPen® (N=9) Epinephrine Film No Prodrug (N=9)
Epinephrine Prodrug (AQST-108) Overcomes Vasoconstriction 18 min Tmax Aquestive’s library of
epinephrine prodrugs can control conversion ratePotential to: Improve Tmax epinephrineReduce dosageIncrease Cmax AQST-108 (Dipivefrin) sublingual filmStrong, consistent absorptionRapid TmaxRequires faster conversion for improved epinephrine
PK
Introducing AQST-109: 2nd Generation Epinephrine Prodrug Attribute Relative to AQST-108 Permeation
Rate Increased Conversion Rate Increased Required Dose Decreased Tolerability Increased MiniPig data show similar exposure at lower doses Prototypes Epinephrine Cmax (ng/mL) N=5 AQST-108 (24mg) 2.7 AQST-109 (6mg) 3.0 Half
Life AQST-108 AQST-109 Minipig 3.1 0.8 Dog 16.0 NC* Human 10.3 NC* In vitro data showing instant conversion of AQST-109 *Too fast to calculate
Patent Applications Extending into 2041 Innovation Patent Status Permeation enhancers that improve
delivery of epinephrine, PK and PD 1 US application8 Foreign applicationsPriority date: May 5, 2016Possible patent term to 2037 Permeation enhancers that improve delivery of dipivefrin and epinephrine, PK and PD 2 US applications8 Foreign
applicationsPriority date: May 4, 2017Possible patent term to 2037 Prodrugs of epinephrine and permeation enhancers, conversion rates, PK and PD 2 US applications1 Foreign applicationPriority date: late 2019Possible patent term to 2041
John Oppenheimer, MD Anaphylaxis and EpinephrineClinical Lessons From Today’s Injectable Products
Introduction John Oppenheimer, M.D.UMDNJ Rutgers University School of MedicinePulmonary & Allergy
Associates
Indirect and observational evidence of effectiveness1There are no randomized, placebo-controlled efficacy
and safety studies in patientsCochrane Collaboration confirmed this finding2 PK and PD comparability is importantThere is no ethical clinical model for anaphylaxis Epinephrine Is Effective PK, pharmacokinetic; PD, pharmacodynamic.1.
Lieberman P et al. Ann Allergy Asthma Immunol. 2015;115:341-384; 2. AAAAI online website. March 29, 2018. Accessed March 9, 2021. https://www.aaaai.org/global/latest-research-summaries/New-Research-from-JACI-In-Practice/epinephrine
Optimal Dose is Unknown1 No data to support the “correct dose”1 In adults, a higher dose was previously
well accepted1 Dose-ranging and optimal dose selection for the FDA-approved EAI products2 EAI, epinephrine auto-injector; FDA, US Food and Drug Administration.1. Lieberman P et al. Ann Allergy Asthma Immunol. 2015;115:341-384; 2. EpiPen.
Prescribing information. Mylan Specialty LP; 2020;
Injected EpinephrinePK and PD Considerations PK and PD data from epinephrine administered via injection
are sparsePublished studies suggest a wide variation in Cmax and Tmax1 IM, intramuscular.1. Dworaczyk D, Hunt A. Presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) National Conference, March 16, 2020.
https://brynpharma.com/media/content/docs/comparative-delivery-poster.pdf; 2. Dworaczyk D, Hunt J Allergy Clin Immunol Pract. 2021;147(2):(2 suppl)AB241 Presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) National
Conference; March 16, 2020; Accessed March 2, 2021. 3. Worm M et al. Clin Transl Allergy. 2020;10:21; 4. Duvauchelle T et al. J Allergy Clin Immunol Pract. 2018;6(4):1257-1263; 5. Breuer C et al. Eur J Clin Pharmacol. 2013;69:1303-1310; 6. US
FDA Epinephrine (Auvi-Q) clinical pharmacology and Biopharmaceutics review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000ClinPharmR.pdf. Accessed on February 25, 2021; 7. Edwards ES et al. Ann Allergy Asthma Immunol.
2013;111(2):132-137. Author, year Device Mean Cmax (pg/mL) Mean Tmax(min) Dworaczyk and Hunt, 20201 EpiPen 0.3 mg 308 16 Dworaczyk and Hunt, 20212 EpiPen 0.3 mg 288 10 Worm M et al, 20203 EpiPen 0.3 mg 520b,d 9c IM injection
0.3 mg 310a,b 40c Duvauchelle T et al, 20184 Anapen 0.3 mg 377 12d Breuer C et al, 20135 Anapen 0.3 mg 484b 13d Auvi-Q FDA Review6Edwards et al 20137 Auvi-Q 0.3 mg 486 20d EpiPen 0.3 mg 520 10d aNanogram to
picogram converted; buncorrected values; cmedian value; dconverted to minutes from hours.
Variability of Epinephrine Injected Into Muscle Data on file from Study 200203 top line results. Mean
(±SD) baseline corrected epinephrine concentration over scheduled timeby treatment, linear scale 6005004003002001000 Concentration (pg/mL) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 (0.3-mg IM injection) Time (h)
Increase in systolic blood pressure Increase in diastolic blood pressure Increase in heart rate Known
Pharmacodynamic (PD) Markers for Epinephrine Simons FE. J Allergy Clin Immunol. 2009;124(4):625-636.
Key PK Measures Based on Approved Products1-7 Cmax range280 pg/mL–530 pg/mLMedian Tmax range<20
min 1. Dworaczyk D, Hunt A. Presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) National Conference, March 16, 2020. https://brynpharma.com/media/content/docs/comparative-delivery-poster.pdf; 2. Dworaczyk D, Hunt J
Allergy Clin Immunol Pract. 2021;147(2):(2 suppl)AB241 Presented at the American Academy of Allergy, Asthma and Immunology (AAAAI) National Conference; March 16, 2020; Accessed March 2, 2021. 3. Worm M et al. Clin Transl Allergy. 2020;10:21; 4.
Duvauchelle T et al. J Allergy Clin Immunol Pract. 2018;6(4):1257-1263; 5. Breuer C et al. Eur J Clin Pharmacol. 2013;69:1303-1310; 6. US FDA Epinephrine (Auvi-Q) clinical pharmacology and Biopharmaceutics review.
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/201739Orig1s000ClinPharmR.pdf. Accessed on February 25, 2021; 7. Edwards ES et al. Ann Allergy Asthma Immunol. 2013;111(2):132-137.
Dose levels for epinephrine have been established through decades of clinical experience rather than
via efficacy studiesStudies have shown a wide variation in PK results after injecting epinephrinePD markers for epinephrine are well establishedFor injected epinephrine products, an expected range for Cmax and Tmax can be established from the
literature Summary
Dr. Mark LeporeChief Medical OfficerAllergy Therapies Anaphylaxis and EpinephrineAQST-108 and AQST-109:
Clinical Overview
A Brief Introduction Dr. Mark LeporeChief Medical Officer, Allergy TherapiesTrained in general
pediatrics and allergy/clinical immunologyFellow of AAAAI 10 years experience in private practice as a clinical investigator Teva Global Respiratory R&D and US Medical AffairsLupin R&D, Inhalation and Complex Injectable ProductsFather
of 3 food-allergic children
Aquestive’s Approach for Sublingual Film Delivery Absorption(via prodrugs)Conversion(into
epinephrine) +
AQST-108: Clinical Trials Review Protocol 2002037-period, 4-treatment (with replication of 3
treatments), 3-sequence crossoverTest–24 mg dipivefrin sublingual filmRef 1–0.3 mg SC epinephrineRef 2–0.3 mg IM epinephrineSafety–0.5 mg SC epinephrine (not replicated, period 7)28 subjects enrolledPK and PD measurementsFrequent sampling from
pre-dose to 240 minutes post-dose Protocol 180299Single-ascending dose study in healthy young male volunteers*Part 1–dose levels of 0.6 mg, 3 mg, 6 mg, 12 mg, 24 mg, 30 mg, and 36 mg6-12 subjects per dose levelPK and PD measurementsFrequent
sampling from pre-dose to 240 minutes post-dose *Also referred to as a proof of concept or dose-escalation study.
AQST-108: Rapid and Extensive Absorption* Description -203 -299 Cmax (pg/mL) 1276 1487 AUC 0-t
(hr*pg/mL) 425 480 Tmax (min) 18 20 Tmax range (min) 10-40 15-34 * Compared with IM or SQ injected epinephrine **Represents 203 data from top line results. Time (hr) Dipivefrin Concentration (pg/mL) 20 min 18 min P200203,
Test ** P180299, Test
AQST-108: Conversion into Epinephrine Systemically * Represents data from top-line
results. Description -203 -299 Cmax (pg/ml) 205 261 AUC 0-t (hr*pg/ml) 332 497 Tmax (min) 40 28 Tmax Range (min) 11 - 106 20 - 60 Time (hr) Concentration (pg/mL) P200203, Test P180299, Test
AQST-108: Compelling Pharmacodynamic (PD) Results When Compared to Epinephrine IM Injection *Represents
data from top-line results.SBP=Systolic Blood Pressure AQST-108 AQST-108 0.3mg IM IM Concentration (pg/mL) Concentration (pg/mL) Time (hr) Epinephrine Mean ConcDipivefrin Mean ConcSBP Time (hr) Epi ConcentrationSBP AUCT
SBP (hour* mmHg) Treatment
AQST-108: Critical Insights from Conversion Rate *Represents data from top-line
results. Description AQST-108 SQ Injection IM Injection Cmax (pg/mL) 205 388 475 AUC 0-t (hr*pg/mL) 332 551 483 Tmax (min) 40 31 30 Tmax Range (min) 11-106 8-68 4-75 Time (hr) Concentration (pg/mL) P200203, TestP200203,
Ref 1P200203, Ref 2P180299, 24 mg
Epi SF AQST-108Dipivefrin AQST-109 Epinephrine/Prodrug Development
Progression Study160445 Studies180299200203
Part 25-period crossoverN=12Repeat of 1 formulation at target dose from part 11-2 optimized
formulations1 dosing administration change1 RLD (0.3 mg IM injection) AQST-109 Designed to Minimize Conversion Time Cohort 10.6 mg/mL SL drops Part 1Single-ascending dose (SAD)N=6 per cohort Cohort 21.2 mg/mL SL drops Cohort 33 mg SL
film (formulation 1) Cohort 4-7 (1 per formulation)4 formulations of SL filmDose escalation 6 mg, 12 mg, 18 mg, 24 mg 1 2 3 4 Established targetdose from Part 1
Summary Aquestive’s AQST-108 has demonstratedRapid and extensive absorptionConversion to epinephrine,
but slower than desiredCompelling changes in PD measuresNext steps Advance AQST-109 into PK trialsMeet with FDA to discuss AQST-108 PD results and next steps
Anaphylaxis and EpinephrineR&D Day: Summary March 25, 2021
Clinical/Regulatory Timeline – 2 “shots on goal” Single dose ascending study completed in H2 2019FDA
pre-IND meeting completed in H1 2020FDA fast track designation received in H1 2020Phase 1 crossover study completed in H2 2020Anticipate FDA meeting in H2 2021 AQST-108 sublingual film First in Humans (FIH) Study dossier submitted to Health
Canada; following study, anticipate:FIH Study read-out in H2 2021FDA pre-IND meeting in H2 2021Opening IND in early 2022 AQST-109 sublingual film The Clinical Trial Application (CTA) is under review. Should Health Canada (HC) request
additional information, the study timelines may be impacted. There can be no assurance that HC will take action on the CTA in a timely fashion. Anticipate:Conducting pilot and pivotal PK studies in 2022Conducting human factors study in
2022Pre-NDA meeting with FDA end 2022
Key Takeaways Large unmet need and a growing patient population AQST-108 and AQST-109 represent
compelling opportunities for the oral delivery of epinephrineThere is a known FDA pathway to approval
Exhibit 99.2
Aquestive Therapeutics Successfully Demonstrates Repeatable and Predictable Oral Sublingual Film Administration of Epinephrine
| • |
Provides in-depth scientific and clinical data in R&D event today at 9:00 am ET
|
| • |
Outlines data from two completed Phase 1 pharmacokinetic (PK) trials for AQST-108 (dipivefrin) sublingual film
|
| • |
Articulates development strategy for second prodrug candidate, AQST-109 sublingual film
|
| • |
Provides details on potential patent coverage to at least 2037
|
Warren, NJ, March 25, 2021 – Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical company focused on developing and commercializing differentiated products that address patients’ unmet needs and solve
therapeutic problems, will provide later this morning an in-depth overview of its systemic epinephrine drug delivery program combining its novel prodrug technology and its PharmFilm® technology. At the R&D event, the management team and KOLs
will share an extensive review of the science, clinical results, and development strategy associated with two prodrug candidates in development for the treatment of allergic reactions including anaphylaxis. Aquestive has submitted multiple U.S.
and foreign patent applications that cover the technology and formulations for its two prodrug candidates, AQST-108 and AQST-109. If granted, Aquestive anticipates patent protection for both drug candidates through at least 2037.
“Aquestive is, we believe, the first and only company that has successfully demonstrated a repeatable and predictable capability for orally administering a film for the delivery of systemic epinephrine as indicated
by the results from the two completed Phase 1 PK trials with AQST-108 that will be shared at today’s R&D event,” remarked Dan Barber, Chief Operating Officer of Aquestive. “We have taken the learnings from the AQST-108 studies regarding
absorption and conversion and have applied them to the development of our second generation prodrug, AQST-109. We plan to commence a Phase 1 PK trial with AQST-109 and anticipate a topline data readout in the second half of 2021.”
“Today is an exciting day for the Aquestive team,” said Keith Kendall, President and Chief Executive Officer of Aquestive. “Now that we have completed the submission of our initial patent applications, we are
thrilled to provide our various stakeholders more insight into our scientific and clinical efforts to develop treatments for anaphylaxis. As we will discuss during our R&D event today, patients, caregivers, and healthcare providers remain
highly interested in non-invasive routes of delivery for systemic epinephrine. Our surveys show that 80% of patients surveyed are interested in PharmFilm replacing their current medical device and 96% of patients surveyed believe that PharmFilm
would be easier to administer during an emergency situation when compared to their current medical device.”
AQST-108 Sublingual Film
Aquestive plans to outline in the R&D event today that its “first of its kind” oral sublingual film candidate delivering systemic epinephrine, AQST-108, is composed of the prodrug dipivefrin, which is contained
within a unique polymeric matrix of Aquestive’s PharmFilm technology. Dipivefrin is currently approved by the FDA for ophthalmic indications. Dipivefrin is enzymatically cleaved systemically into epinephrine after administration.
Aquestive previously completed an initial PK trial (Protocol 180299). This study featured a single ascending dose design with between 6-12
healthy subjects completing each dosing level during Part I and Part II of the study. During the study, both PK and pharmacodynamic (PD) markers were measured. At the target dose level, the observed range for time to reach maximal
concentration (Tmax) for AQST-108 was 15-35 minutes, and the observed maximal concentration (Cmax) was 1487 pg/mL. In addition, this study indicated that AQST-108 was rapidly converted to epinephrine with an observed epinephrine Tmax range of
20-60 minutes and an observed Cmax of 261 pg/mL.
Aquestive recently completed its second Phase 1 PK trial in 28 healthy adult subjects, which featured a four-treatment crossover design comparing PK, safety and pharmacodynamics of AQST-108 to that of epinephrine
administered via both subcutaneous and intramuscular injections. In this study, the observed range for Tmax for AQST-108 was 10-40 minutes and the observed Cmax for AQST-108 was 1276 pg/mL. In addition, this study indicated that AQST-108 was
rapidly converted to epinephrine with an observed Tmax range of 11-106 minutes and an observed Cmax of 205 pg/mL. This was compared to an epinephrine Tmax range of 4-75 minutes and 8-68 minutes and Cmax of 475 pg/mL and 388 pg/mL for the
intramuscular and subcutaneous injections, respectively.
In addition, several pharmacodynamic markers were measured during the second Phase 1 PK study. AQST-108 demonstrated changes from baseline in heart rate, systolic blood pressure, and diastolic blood pressure which
are relevant in the context of anaphylaxis treatment and epinephrine’s mechanism of action. For instance, for the area under the effect curve (AUEC) for systolic blood pressure, the median values for AQST-108 and intramuscular injected epinephrine
were 452 and 428 (in hr*mm hg), respectively, indicating a comparable effect from both treatments on systolic blood pressure in healthy volunteers. A similar pattern was demonstrated for other pharmacodynamic measures as well.
Aquestive plans on meeting with the FDA in the second half of 2021 to review these results and discuss next steps in the development of AQST-108.
AQST-109 Sublingual Film
During today’s R&D event, Aquestive will articulate its development strategy for a second epinephrine prodrug candidate, AQST-109 sublingual film. AQST-109 is a next generation prodrug of epinephrine that
Aquestive intends to develop for sublingual treatment of allergic reactions including anaphylaxis. In vitro tests and preclinical studies indicate that AQST-109 has the potential to absorb more extensively, convert more rapidly to systemic
epinephrine, utilize less drug and provide a unique profile when compared to AQST-108. Aquestive anticipates conducting and completing a single ascending dose PK study in the second half of 2021. Based upon receiving favorable topline results from
the study, Aquestive intends to request a pre-IND meeting with the FDA.
Webcast Access/Replay
A webcast of the virtual R&D event today at 9:00 am ET and accompanying slides will be available under “Events and Presentations” in the Investors section of the Company’s website at
https://investors.aquestive.com/events-and-presentations. In addition, the R&D event can be accessed by dialing (833) 640-1722 from the U.S. and (602) 585-9829 internationally, followed by the conference ID: 3598556. The event webcast will be
archived for 30 days.
About Anaphylaxis
Anaphylaxis is a potentially life-threatening systemic allergic reaction, with an estimated incidence of 50 to 112 episodes per 100,000 people per year. The frequency of hospital admissions for anaphylaxis has
increased 500-700% in the last 10-15 years. The most common causes of reactions that can include anaphylaxis are medications, foods (such as peanuts), and venom from insect stings. Epinephrine injection is the current standard of treatment intended
to reverse the potentially severe manifestation of anaphylaxis, which may include red rash, throat swelling, respiratory problems, gastrointestinal distress and loss of consciousness.
About Aquestive Therapeutics
Aquestive Therapeutics is a pharmaceutical company that applies innovative technology to solve therapeutic problems and improve medicines for patients. The Company has commercialized one internally-developed
proprietary product to date, Sympazan® (clobazam) oral film, has a commercial proprietary product pipeline focused on the treatment of diseases of the central nervous system, or CNS, and other unmet needs, and is developing orally administered
complex molecules to provide alternatives to invasively administered standard of care therapies. The Company also collaborates with other pharmaceutical companies to bring new molecules to market using proprietary, best-in-class technologies, like
PharmFilm®, and has proven capabilities for drug development and commercialization.
Forward-Looking Statements
Certain statements in this press release include “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “anticipate,” “plan,” “expect,”
“estimate,” “intend,” “may,” “will,” or the negative of those terms, and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include, but are not limited to, statements regarding the
advancement of AQST-108, AQST-109 and other product candidates through the regulatory and development pipeline; and business strategies, market opportunities, and other statements that are not historical facts. These forward-looking statements are
subject to the uncertain impact of the COVID-19 global pandemic on our business including with respect to our clinical trials including site initiation, patient enrollment and timing and adequacy of clinical trials; on regulatory submissions and
regulatory reviews and approvals of our product candidates; pharmaceutical ingredient and other raw materials supply chain, manufacture, and distribution; sale of and demand for our products; our liquidity and availability of capital resources;
customer demand for our products and services; customers’ ability to pay for goods and services; and ongoing availability of an appropriate labor force and skilled professionals. Given these uncertainties, the Company is unable to provide
assurance that operations can be maintained as planned prior to the COVID-19 pandemic.
These forward-looking statements are based on our current expectations and beliefs and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in
the forward-looking statements. Such risks and uncertainties include, but are not limited to, risks associated with the Company's development work, including any delays or changes to the timing, cost and success of our product development
activities and clinical trials and plans for AQST-108, AQST-109 and our other drug candidates; risk of delays in FDA approval of our drug candidates Libervant, AQST-108, AQST-109 and our other drug candidates or failure to receive approval; ability
to address the concerns identified in the FDA’s Complete Response Letter dated September 25, 2020 regarding the New Drug Application for Libervant; risk of our ability to demonstrate to the FDA “clinical superiority” within the meaning of the FDA
regulations of Libervant relative to FDA-approved diazepam rectal gel and nasal spray products including by establishing a major contribution to patient care within the meaning of FDA regulations relative to the approved products as well as risks
related to other potential pathways or positions which are or may in the future be advanced to the FDA to overcome the seven year orphan drug exclusivity granted by the FDA for the approved nasal spray product of a competitor in the U.S. and there
can be no assurance that we will be successful; risk that a competitor obtains FDA orphan drug exclusivity for a product with the same active moiety as any of our other drug products for which we are seeking FDA approval and that such earlier
approved competitor orphan drug blocks such other product candidates in the U.S. for seven years for the same indication; risk inherent in commercializing a new product (including technology risks, financial risks, market risks and implementation
risks and regulatory limitations); risk of development of our sales and marketing capabilities; risk of legal costs associated with and the outcome of our patent litigation challenging third party at risk generic sale of our proprietary products;
risk of sufficient capital and cash resources, including access to available debt and equity financing and revenues from operations, to satisfy all of our short-term and longer term cash requirements and other cash needs, at the times and in the
amounts needed; risk of failure to satisfy all financial and other debt covenants and of any default; our and our competitors’ orphan drug approval and resulting drug exclusivity for our products or products of our competitors; short-term and
long-term liquidity and cash requirements, cash funding and cash burn; risk related to government claims against Indivior for which we license, manufacture and sell Suboxone® and which accounts for the substantial part of our current operating
revenues; risks related to the outsourcing of certain marketing and other operational and staff functions to third parties; risk of the rate and degree of market acceptance of our product and product candidates; the success of any competing
products, including generics; risk of the size and growth of our product markets; risks of compliance with all FDA and other governmental and customer requirements for our manufacturing facilities; risks associated with intellectual property rights
and infringement claims relating to the Company's products; risk of unexpected patent developments; the impact of existing and future legislation and regulatory provisions on product exclusivity; legislation or regulatory actions affecting
pharmaceutical product pricing, reimbursement or access; claims and risks that may arise regarding the safety or efficacy of the Company's products and product candidates; risk of loss of significant customers; risks related to legal proceedings,
including patent infringement, investigative and antitrust litigation matters; changes in government laws and regulations; risk of product recalls and withdrawals; uncertainties related to general economic, political, business, industry, regulatory
and market conditions and other unusual items; and other uncertainties affecting the Company described in the “Risk Factors” section and in other sections included in our Annual Report on Form 10 K, in our Quarterly Reports on Form 10-Q, and in our
Current Reports on Form 8-K filed with the Securities Exchange Commission (SEC). Given those uncertainties, you should not place undue reliance on these forward-looking statements, which speak only as of the date made. All subsequent
forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. The Company assumes no obligation to update forward-looking statements or outlook or guidance
after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by applicable law.
PharmFilm®, Sympazan® and the Aquestive logo are registered trademarks of Aquestive Therapeutics, Inc. All other registered trademarks referenced herein are the property of their respective owners.
Investor inquiries:
Westwicke, an ICR Company
Stephanie Carrington
stephanie.carington@westwicke.com
646-277-1282