Aquestive Therapeutics, Inc. · NASDAQ:AQST
Aquestive Therapeutics — Investor Day (March 2021)
62 slides from Aquestive Therapeutics's investor day presentation, Mar 25, 2021
Slide 1: Anaphylaxis and Epinephrine R&D Day March 25, 2021
Anaphylaxis and EpinephrineR&D Day March 25, 2021
Slide 2: Forward Looking Statement
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 expres
Slide 3: Today's Agenda
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
Slide 4: PharmFilm Technology – Where You Need It, When You Need It
PharmFilm® Technology – Where You Need It, When You Need It™ And Needle Free
Slide 5: Anaphylaxis and Epinephrine: Medical Overview
David M. Fleischer, MD, FAAAAIProfessor of PediatricsSection Head, Allergy and ImmunologyChildren’s Hospital ColoradoUniversity of Colorado Denver School of Medicine Anaphylaxis and EpinephrineMedical Overview
Slide 6: Introduction: David M. Fleischer, MD
Introduction David M. Fleischer, MD, FAAAAIProfessor of PediatricsSection Head, Allergy and ImmunologyChildren’s Hospital ColoradoUniversity of Colorado Denver School of Medicine
Slide 7: Defining Anaphylaxis
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
Slide 8: Common Triggers of Anaphylaxis
Common Triggers of Anaphylaxis Idiopathic anaphylaxis Exercise Insect venom, medications, and latex
Slide 9: Common Signs and Symptoms of Anaphylaxis
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 i
Slide 10: Patterns of Anaphylaxis
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 reactionPro
Slide 11: Epinephrine is first-line treatment for anaphylaxis
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
Slide 12: Use and Carry Practices for Epinephrine Auto-Injectors
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
Slide 13: Adverse Events Due to Incorrect Use of EAIs
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 media
Slide 14: EAI Refill Rates Are Suboptimal
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 y
Slide 15: Summary
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 pa
Slide 16: Anaphylaxis and Epinephrine Market Overview
Michael Arcara Anaphylaxis and EpinephrineMarket Overview
Slide 17: Introduction: Michael Arcara
Introduction Michael ArcaraCommercial Lead, AllergyMBA, University of Michigan25 years experience in pharmaceutical commercial developmentEpinephrine-specific experience: Mylan (EpiPen); Valeant (Emerade)
Slide 18: Epidemiology: Life-Threatening Allergic Reaction
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 typ
Slide 19: Overview: Epinephrine Market
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 u
Slide 20: Physician Research: Preference for Alternative Route of Administration
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 ep
Slide 21: Physician Research: Concerns About Patients Having EAI
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, p
Slide 22: Patient Survey: Unprompted Unmet Need
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?
Slide 23: Patient Survey: First Exposure to Film Dosing
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
Slide 24: Patient Survey: Impact, Epinephrine On Hand
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
Slide 25: Patient Survey: Ask Doctor About Film
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
Slide 26: Our View of the Epinephrine Commercial Opportunity
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
Slide 27: Aquestive PharmFilm – Potential Annual Peak Net Sales
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 (
Slide 28: Summary: Anaphylaxis and Epinephrine
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 repre
Slide 29: Aquestive Epinephrine Program
Stephen Wargacki, Ph.D.Vice President R&D Anaphylaxis and EpinephrineAquestive Epinephrine Program
Slide 30: Introduction: Stephen Wargacki, PhD
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)
Slide 31: Challenges of Epinephrine for Anaphylaxis
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
Slide 32: Noninvasive Delivery of Epinephrine
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 Unstabl
Slide 33: PharmFilm for Delivery of Oral Epinephrine
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]
Slide 34: Uses of Prodrugs in Pharmaceuticals
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 anot
Slide 35: AQST-108: L-Dipivefrin
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
Slide 36: Impact of AQST-108 on Sublingual Delivery of Epinephrine
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)
Slide 37: Epinephrine Prodrug (AQST-108) Overcomes Vasoconstriction
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 co
Slide 38: Introducing AQST-109: 2nd Generation Epinephrine Prodrug
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 AQS
Slide 39: Patent Applications Extending into 2041
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,
Slide 40: Clinical Lessons From Today's Injectable Products
John Oppenheimer, MD Anaphylaxis and EpinephrineClinical Lessons From Today’s Injectable Products
Slide 41: Introduction: John Oppenheimer, MD
Introduction John Oppenheimer, M.D.UMDNJ Rutgers University School of MedicinePulmonary & Allergy Associates
Slide 42: Epinephrine Is Effective
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, p
Slide 43: Optimal Dose is Unknown
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 Ast
Slide 44: Injected Epinephrine PK and PD Considerations
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) Nationa
Slide 45: Variability of Epinephrine Injected Into Muscle
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) T
Slide 46: Known Pharmacodynamic (PD) Markers for Epinephrine
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.
Slide 47: Key PK Measures Based on Approved Products
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-
Slide 48: Summary
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 fo
Slide 49: AQST-108 and AQST-109: Clinical Overview
Dr. Mark LeporeChief Medical OfficerAllergy Therapies Anaphylaxis and EpinephrineAQST-108 and AQST-109: Clinical Overview
Slide 50: A Brief Introduction: Dr. Mark Lepore
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 Comp
Slide 51: Aquestive's Approach for Sublingual Film Delivery
Aquestive’s Approach for Sublingual Film Delivery Absorption(via prodrugs)Conversion(into epinephrine) +
Slide 52: AQST-108: Clinical Trials Review
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 P
Slide 53: AQST-108: Rapid and Extensive Absorption
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
Slide 54: AQST-108: Conversion into Epinephrine Systemically
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
Slide 55: AQST-108: Pharmacodynamic Results vs Epinephrine IM Injection
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) Ep
Slide 56: AQST-108: Critical Insights from Conversion Rate
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,
Slide 57: Epinephrine/Prodrug Development Progression
Epi SF AQST-108Dipivefrin AQST-109 Epinephrine/Prodrug Development Progression Study160445 Studies180299200203
Slide 58: AQST-109 Designed to Minimize Conversion Time
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
Slide 59: Summary
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
Slide 60: R&D Day: Summary
Anaphylaxis and EpinephrineR&D Day: Summary March 25, 2021
Slide 61: Clinical/Regulatory Timeline – "shots on goal"
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 Human
Slide 62: Key Takeaways
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