Aquestive Therapeutics, Inc. · NASDAQ:AQST
Aquestive Therapeutics — Investor Day (September 2024)
54 slides from Aquestive Therapeutics's investor day presentation, Sep 27, 2024
Slide 1: Adrenaverse Prodrug Platform Investor Day
Adrenaverse Prodrug Platform Investor Day September 27, 2024
Slide 2: Disclaimer
Disclaimer 2 © 2024 Aquestive Therapeutics, Inc. This presentation and the accompanying oral commentary have been prepared by Aquestive Therapeutics, Inc. (“Aquestive”, the “Company”, “our” or “us”) and contains forward-looking statements within the meaning of the Private Securities Litigation Refor
Slide 3: Today's agenda
Today’s agenda Topic Presenters Introductions and company overview Dan Barber Chief Executive Officer Aquestive Therapeutics Scientific overview of adrenergic receptors J. David Farrar, PhD Associate Professor Immunology/Molecular Biology UT Southwestern Medical Center AdrenaverseTM prodrug platform
Slide 4: PharmFilm Drug delivery technologies and Adrenaverse Prodrug Platform
PharmFilm® 4 Drug del very technologies AdrenaverseTM Prodrug Platform Adrenaverse platform contains a library of over 20 epinephrine prodrugs that demonstrate control of absorption and conversion rates across a variety of dosage forms and delivery sites, including allergy, topical (dermatological),
Slide 5: Diversified pipeline
Diversified pipeline 5 1. Annual revenue includes revenue for patients 12 and up after launch in 2027. 2. Aquestive Therapeutics data on file.
Slide 6: Growth plan
Growth plan 6 1. Assumes satisfaction of all predetermined clinical endpoints and approved by U.S. Food and Drug Administration (FDA). 2. Estimate is based on an orphan drug market exclusivity block until January of 2027 by an FDA approved nasal spray product. 20261 Launch Anaphylm2024 Launch Liberv
Slide 7: Anaphylm (epinephrine) Sublingual Film
Anaphylm (epinephrine) Sublingual Film + + Easy To Carry Easy To Administer Works Quickly1 7 1. Aquestive Therapeutics data on file. Anaphylm is the first and only non-device based, orally delivered epinephrine product candidate
Slide 8: Anaphylm is fast-acting and well-tolerated, with safety comparable to standard of care
Anaphylm is fast-acting and well-tolerated, with a safety profile comparable to standard of care (SOC)1 8 1 2 3 Rapid absorption as demonstrated by: Consistent pharmacokinetics (PK) demonstrated across 5 administration procedures: Consistent time to peak drug concentration (Tmax) of 12-15 minutes On
Slide 9: Expected clinical timeline for Anaphylm
Expected clinical timeline for Anaphlym 9 Q2 2024 Q3 2024 Q4 2024 Q1 2025 Temperature/pH Study Completed Oral Allergy Syndrome (OAS) Study Self-Administration Study Completed Pre-NDA Meeting File NDA Pediatric Study
Slide 10: Our thesis (the big idea)
Our thesis (the big idea) 10 Human Skin Structure • The utility of exogeneous epinephrine for the treatment of medical conditions has been limited due to the molecule’s five- minute half-life as well as poor absorption capabilities¹ • Aquestive’s Adrenaverse technology unlocks the potential of epine
Slide 11: Scientific Overview of Adrenergic Receptors
Scientific Overview of Adrenergic Receptors Dr. J. David Farrar
Slide 12: J. David Farrar, PhD
J. David Farrar, PhD • Associate Professor • UT Southwestern Medical Center, Dallas, TX • PhD in Immunology • 53 Publications with >4000 citations • Specializes in neural regulation of immune function
Slide 13: Epinephrine and Norepinephrine regulate key biological functions
13 Adrenaline (Epinephrine) Noradrenaline (Norepinephrine) Physiological Regulation • Digestion • Body temperature • Blood pressure • Heart rate • Breathing • “Fight or Flight” response Effects on Immune Cells • Pathogen recognition • Antibody production • Immune cell trafficking • General immune su
Slide 14: Adrenergic signaling suppresses inflammatory processes
14 Effects on Immune Cells • Pathogen recognition • Antibody production • Immune cell trafficking • General immune suppression Signaling through the adrenergic receptor suppresses a variety of inflammatory processes¹ Innate immune cells • Macrophages • Neutrophils • Mast cells • Dendritic cells • Na
Slide 15: Epinephrine is a potent inhibitor of inflammatory cytokines in humans
15 Effects on Immune Cells • Pathogen recognition • Antibody production • Immune cell trafficking • General immune suppression Epinephrine is a potent inhibitor of inflammatory cytokines in humans Epinephrine inhibits endotoxin-induced IL- 1beta production; roles of tumor necrosis factor – alpha and
Slide 16: Epinephrine is a potent inhibitor of inflammatory cytokines in mouse models
16 Effects on Immune Cells • Pathogen recognition • Antibody production • Immune cell trafficking • General immune suppression Epinephrine is a potent inhibitor of inflammatory cytokines in mouse models¹ The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion Norepinephrine
Slide 17: ADRB2-mediated suppression of inflammation
17 Effects on Immune Cells • Pathogen recognition • Antibody production • Immune cell trafficking • General immune suppression Adrenergic receptor beta 2 (ADRB2)-mediated suppression of inflammation Adrenergic regulation of immune cell function and inflammation1 1. Drashya Sharma, J. David Farrar ,
Slide 18: Key takeaways
18 Effects on Immune Cells • Pathogen recognition • Antibody production • Immune cell trafficking • General immune suppression Key takeaways • Epinephrine and Norepinephrine are natural immune modulators that act both systemically and locally to inhibit the magnitude of normal inflammation • Pharmac
Slide 19: Adrenaverse Prodrug Platform R&D Overview
Stephen Wargacki, Ph.D. Chief Science Officer Adrenaverse Prodrug Platform R&D Overview
Slide 20: Stephen Wargacki, PhD
20 Stephen Wargacki, PhD Chief Science Officer • PhD, Polymer Chemistry University of Tennessee • Postdoctoral Fellow Air Force Research Laboratory • 15+ years experience in alternative drug delivery • 29 publications (414 citations) • 122 patents/applications (26 patent families)
Slide 21: Adrenaverse: A robust and versatile prodrug platform
Adrenaverse : A robust and versatile prodrug platform Drug bounded to another molecule for improved properties Aquestive’s topical platform allows for: • Simple fast drying formulations • Ability to accommodate single or multiple prodrugs • Ability to include additional components without impacting
Slide 22: Non-clinical results (pharmacokinetics in rat ears)
Non-clinical results (pharmacokinetics in rat ears)¹ Drug bounded to another molecule for improved properties Drug released by metabolic processes 22 0 50000 100000 150000 200000 250000 300000 350000 1% 2.50% Ep in ep hr in e (n g/ g) AQST-108 Conc. (wt%) Epinephrine exposure after application to ra
Slide 23: Non-clinical PK results in minipigs
Non-clinical pharmacokinetic (PK) results in minipigs¹ Drug bounded to another molecule for improved properties Drug released by metabolic processes 23 0 1000 2000 3000 4000 0 1 2 3 4 5 6 7 Co nc en tra tio n (n g/ g) time (hours) Tissue concentrations of AQST-108 in the dermis of minipigs Epinephri
Slide 24: Passive cutaneous anaphylaxis in rat ears
Non-clinical results - passive cutaneous anaphylaxis in rat ears¹ • N=10 rats per group (except N=5, naïve control) were given either topical application of: Placebo, 1% or 2.5% AQST-108 was applied, high dose oral histamine (desloratadine) as positive control • Injection of 2,4-dinitrophenol (DNP),
Slide 25: Ex-Vivo human skin microdialysis
Ex-Vivo human skin microdialysis Vehicle + PBS 2.5% AQST-108 + PBS 10% AQST-108 + PBS Vehicle + anti-IgE 2.5% AQST-108 + anti-IgE 10% AQST-108 + anti-IgE Ex vivo skin explant with sampling lanes 1– 6 1 2 3 4 5 6 25 Design: Freshly excised human skin used for microdialysis of interstitial fluid acros
Slide 26: Topical AQST-108 human skin microdialysis results
Topical AQST-108 human skin microdialysis results¹ AQST-108 demonstrates that histamine release is inhibited through mast cell stabilization in ex-vivo human skin provoked with IgE antibodies 26 1. Aquestive Therapeutics data on file.
Slide 27: Cytokine analysis from PCA model
Cytokine analysis from passive cutaneous anaphylaxis (PCA) model¹ 27 AQST-108 demonstrates immunomodulation across multiple cytokines monitored in the PCA model. Graphs represent % cytokine presence during PCA relative to the naive state² 0% 50% 100% 150% 200% 250% KC-GRO placebo 1% 2.50% 0% 20% 40%
Slide 28: Modulation of NK cell activity
Modulation of NK cell activity¹ ritlecitinib³ cortisol 108 Inhibition (IC50) - NK cells 509nM 200nM 750nM 1. Aquestive Therapeutics data on file. 2. IC50 is a measurement of how much of a drug is needed to inhibit a biological process by half. 3. ritlecitnib IC50 extracted from FDA summary basis of
Slide 29: AQST-108 patent applications potentially extending into 2046
AQST-108 patent applications potentially extending into 2046¹ 29 TITLE PATENT STATUS ENHANCED DELIVERY EPINEPHRINE COMPOSITIONS ► Priority date: May 5, 2016 ► Possible patent term to 2037 ENHANCED DELIVERY EPINEPHRINE AND PRODRUG COMPOSITIONS ► Priority date: May 4, 2017 ► Possible patent term to 20
Slide 30: Key takeaways
Key takeaways 30 • AQST-108 non-clinical development demonstrates valuable proof points about absorption and conversion potentially resulting in durable local exposure in the skin without undesirable systemic exposure • Models successfully demonstrated desired pharmacology and immunomodulation that
Slide 31: AQST-108 Topical Gel Initial Indication and Clinical Overview
Dr. Carl Kraus Chief Medical Officer AQST-108 (epinephrine) Topical Gel Initial Indication and Clinical Overview
Slide 32: Carl Kraus, MD
32 Carl Kraus, MD Chief Medical Officer • M.D., Washington University in St. Louis • Residency, University of Chicago • Fellowship, National Institutes of Health • Clinical Reviewer, CDER, FDA • 18+ years experience in multiple therapeutic development programs from preclinical – Phase IV
Slide 33: Human Protein Atlas: clues from receptor expression
The Human Protein Atlas: clues from receptor expression 33 1. Single cell type - ADRB2 - The Human Protein Atlas, ADRB2 – adrenergic receptor beta 2. In addition to high expression on skin tissue, ADRB2 has high expression on immune cells¹
Slide 34: Skin disorders potentially addressable by adrenergic receptor-mediated targeting
Skin disorders potentially addressable by adrenergic receptor- mediated immune cell targeting 34 1. MCAS – mast cell activation syndrome. Granulocytes • Mast cells – Cutaneous mastocytosis, MCAS¹, Alopecia areata • Neutrophils – Chronic granulomatous disease, Leukocyte adhesion deficiencies Natural
Slide 35: Potential indications for Adrenaverse technology
Potential indications for Adrenaverse technology¹ 35 Skin Disorders Psoriasis Atopic Dermatitis Eczema Alopecia areata Vitiligo Mucosal Inflammation Inflammatory Bowel Disease Crohn’s disease COPD/asthma Tumors Tumor microenvironment Tumor associated macrophages Tumor associated bacteria 1. Not yet
Slide 36: Alopecia areata (AA) background
Advancing medicines. Solving problems. Improving lives. Alopecia areata (AA) background¹ 36 1. UpToDate; NAAF.org; BioMedTracker; Benigno et al. A large cross-sectional survey study of the prevalence of AA in the US. 2020; Litfulo Pfizer HCP Page. SALT Evaluation; King et al. Defining severity in Al
Slide 37: Adrenergic receptor agonism may address early AA pathology
Adrenergic receptor agonism may address early AA pathology¹ 37 1. Hair follicle immune privilege and its collapse in Alopecia areata - Bertolini - 2020 - Experimental Dermatology - Wiley Online Library. Goal: restoration of immune privilege Pr o- in fla m m at or y Cy to ki ne s Anti-inflam m atory
Slide 38: Completed first in human two-part study
Completed first in human (FIH) two-part study¹ 38 0.1% (n=4) 0.2% (n=4) 0.4% (n=4) 1.0% (n=4) 2.5% (n=4) Formulation 9 (n=4) Formulation 15 (n=4) Formulation 16 (n=4) si ng le a sc en di ng d os e Part 1 – single ascending doses of a single formulation of AQST-108 Part 2 – a single dose of 1 of 3 fo
Slide 39: AQST-108 planned Phase 2 Alopecia areata clinical study
39 Phase 2a • N=48, 3 doses and placebo • 12 weeks • Trichoscopy evaluations and labs at baseline, 2, 4, 6, 8 & 12 weeks Objectives of Phase 2a Study Assess the safety and efficacy of AQST-108 in Alopecia areata patients following 12 weeks of treatment as determined by digital imagery (Canfield) Obj
Slide 40: Planned AQST-108 clinical and regulatory pathway
Planned AQST-108 clinical and regulatory pathway¹ 40 Q4 2024 Q1 2025 Q2 2025 Q3 2025 Open IND Pre-IND Meeting Phase 2A Phase 2B 1. End of phase 2 meeting with the FDA is planned for the fourth quarter of 2025 or the first quarter of 2026. Request Pre-IND Meeting
Slide 41: Key takeaways
Key takeaways 41 • AQST-108 demonstrated no serious adverse events or topical adverse events • Lack of plasma concentration after application of AQST-108 may indicate conversion in the dermis at the targeted site of action • Plan to hold pre-IND meeting and advance AQST-108 into a Phase 2 clinical s
Slide 42: Alopecia areata Market Potential
Dan Barber Alopecia areata Market Potential
Slide 43: Patient unmet needs in moderate to severe Alopecia areata
Patient unmet needs in moderate to severe Alopecia areata¹ 43 1. Aquestive Therapeutics data on file. Existing JAK inhibitor therapies • are systemic and have known side effects • have a black box warning • only show significant improvement in approximately one out of three cases • have an unaccepta
Slide 44: Alopecia areata represents a potential opportunity
Alopecia areata represents a potential opportunity¹ 44 Reasons to Believe • Patient unmet need is well- documented and understood • Planned development endpoints that are potentially achievable • Competitive landscape indicates pricing will continue to be reasonable (severe is high) • Commercial opp
Slide 45: Alopecia areata occurs in ~2% of the population
Alopecia areata occurs in ~2% of the population 45 1. National Alopecia Areata Foundation, What you need to know about Alopecia areata, https://www.naaf.org/alopecia-areata, Accessed August 2024; 2. National Organization for Rare Disorders, Alopecia areata, https://rarediseases.org/rare-diseases/alo
Slide 46: Currently marketed products for severe AA are JAK inhibitors
Currently marketed products for severe AA are JAK inhibitors Alopecia areata Treatment Landscape1 Product/ Generic Company Mechanism of Action2 Route of Administration2 Dosing Frequency5 Approval Year (Indication)3 Monthly Treatment Cost (WAC)4 O n- La be l B ra nd ed Th er ap ie s JAK1/2 inhibitor
Slide 47: JAK inhibitors pricing for severe AA remains high
JAK inhibitors pricing for severe AA remains high 47 1. Lilly, How much should I expect to pay for Olumiant?; https://pricinginfo.lilly.com/Olumiant, accessed August 2024; 2.Redbook, Accessed August 2024. List Price (WAC, 4mg tablets): $5,480/ month1,2 Indication(s): Adults with Severe Alopecia; Mod
Slide 48: Estimated $1 billion+ opportunity for JAK inhibitors
Estimated $1 billion+ opportunity for JAK inhibitors¹ 48 • Olumiant label for AA granted in June 2022 • Litfulo label for AA granted in June 2023 • Combined prescriptions for Olumiant and Litfulo in 2nd quarter of 2024 totaled ~30K, representing a small fraction of the severe AA patient population •
Slide 49: AQST-108 potential annual peak net sales
AQST-108 – potential annual peak net sales¹ $500M$250M 1. Aquestive Therapeutics data on file; potential revenues are Aquestive Therapeutics estimates based on current information; peak year sales are assumed ~5 years post launch. • In combination with JAK inhibitors • Used ~50% of time when a JAK T
Slide 50: Alopecia areata competitive pipeline
Late-stage pipeline assets of competitors include multiple JAK inhibitor products, creating a unique space for AQST-108, if approved by FDA Alopecia areata competitive pipeline1 Route of Administration JAK Inhibitors Other Mechanism of Actions (MOAs) Phase 3 FiledPhase 2Phase 1 Daxdilimab Immune Sys
Slide 51: Planned commercialization would focus on a derm call point
Planned commercialization efforts would focus on a derm call point 51 Estimated 11,000 dermatologists in the US¹ represents a focused, specialty call point for AQST-108 Potential follow-on indications for AQST-108 (e.g., vitiligo, atopic dermatitis, acne) are also dermatology call points – could cre
Slide 52: Final key takeaways
Final key takeaways • The Adrenaverse platform opens a new development pipeline for the Company • AQST-108 for Alopecia areata has the potential to be an important opportunity 52
Slide 53: Closing Remarks and Q&A
< Aquestive’ Closing Remarks and Q&A
Slide 54: Thank You
< Aquestive: Thank You
Aquestive Therapeutics — Investor Day (September 2024) on 6ix