Aquestive Therapeutics, Inc. · NASDAQ:AQST
Aquestive Therapeutics — Technical Presentation (December 2019)
46 slides from Aquestive Therapeutics's technical presentation, Dec 9, 2019
Slide 1: Investor and Analyst Update on LIBERVANT
Investor and Analyst Update on LIBERVANT™ December 9, 2019
Slide 2: Forward Looking Statement
Forward Looking Statement 2 Certain statements in this presentation and associated oral statements made by management may constitute "forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” "anticipate," "plan," "expect," "esti
Slide 3: Welcome
Welcome 3 Requested an accelerated review, which is not guaranteed but, if granted, on track to potentially launch in early July* Commercial-stage, specialty pharmaceutical company with comprehensive capabilities to advance medicines from pipeline to market Completed rolling submission of New Drug A
Slide 4: Program Overview
Program Overview Gary Slatko, MDChief Medical Officer
Slide 5: Agenda
5 Agenda Topic Time Speaker Opening Remarks 4:00 pm Keith Kendall Program Overview Gary Slatko, MD Treatment Landscape for Epilepsy Rescue: The Unmet Need 4:10 pm Lawrence J. Hirsch, MD LIBERVANT Clinical Development Program: Key Studies and Findings Early-Phase Program Healthy Volunteer Studies Wit
Slide 6: LIBERVANT Development: Overview
6 Key challenges: comparability, safety, and usability Robust clinical development programHealthy volunteer studiesPatient studiesIn-clinic single doseOutpatient chronic, repeated useKey findingsFavorable pharmacologyValidated weight-based dosing regimenComparable diazepam exposure to reference list
Slide 7: Today's Program
Today’s Program ClinicalPK Comparative PK Outpatient Safety & Administration Practice Dr. HirschHow many patients Treatments availableWhat patients needNew options Seizure RescueTreatmentLandscape Dr. HellerHealthy subject studiesDose proportionalityWeight-based regimenBioavailabilityReliability of
Slide 8: Treatment Landscape for Epilepsy Rescue: The Unmet Need
Treatment Landscape for Epilepsy Rescue: The Unmet Need Lawrence J. Hirsch, MDProfessor of NeurologyYale UniversityNew Haven, Connecticut
Slide 9: Definitions
Definitions Clinically and in the literature, the most commonly used definitions for cluster seizures are:2-3 seizures occurring within 24 hours2 seizures occurring within 6 hoursStatistical definitions (prevalence usually lower with these)3-4 times the patient’s usual seizure rateDiffering from a P
Slide 10: Prevalence of Cluster Seizures
Prevalence of Cluster Seizures(2-3 seizures within 6-24 hours; not necessarily distinguishable from habitual seizures) Best estimate after a literature review and our prospective trial1Patients with refractory epilepsy (ongoing seizures at any rate)40% will have a cluster seizure in a given year3.2
Slide 11: Consequences of Cluster Seizures
Consequences of Cluster Seizures, From a Review1 of Retrospective Studies Higher risk of status epilepticus, emergency department (ED) visits, injury, loss of work/study, lower quality of life (QOL) for patient and caregiver, and possibly higher mortality if cluster seizures occur while on treatment
Slide 12: Prospective Study of Rescue Medication Use for Cluster Seizures
Prospective Study of Rescue Medication Use for Cluster Seizures1 Rescue medication useOnly 28% of patients with active epilepsy had a rescue medication prescribedIncluding only 15% of those in the intermediate-risk group, even though 30% went on to have cluster seizuresDuring the year-long study fol
Slide 13: Why Are Rescue Medications So Underused?
Why Are Rescue Medications So Underused? Per the literatureNo seizure action plan in usePoor physician–patient communicationConcerns about limited route(s) of administration For adultsLack of an approved nonrectal option (until late 2019)No one who can administer rescue medication 13
Slide 14: Rescue Therapies Currently Available in the United States
Rescue Therapies Currently Available in the United States Rectal diazepam (Diastat): only approved option until late 2019Oral lorazepam (Ativan); clonazepam, including clonazepam ODT (orally disintegrating tablets); similar medications (but slow onset)Nasal midazolam: approved and recently introduce
Slide 15: Systematic Review of Benzodiazepines for Seizure Emergencies
Systematic Review of Benzodiazepines for Seizure Emergencies1 Broader inclusion, 75 studiesConclusions: for out-of-hospital use, buccal, IN, and IM are all comparable and better options than rectal or IV Time to Seizure Cessation Following Drug Administration IM, intramuscular; IN, intranasal; IV, i
Slide 16: Improving Treatments for Cluster Seizures
16 Although benzodiazepines are considered the treatment of choice for terminating cluster seizures,1,2 currently available drug formulations are suboptimal in terms of:Onset of actionDosing accuracyPortabilityEase of administrationRoute of administration1,3,4 Ideal properties of a pharmacologic age
Slide 17: New Treatment Advances to the Rescue!
New Treatment Advances to the Rescue! Company UCB Aquestive Neurelis Engage Ther. Xeris Pharma Epalex Corp. Crossject Product Nayzilam LIBERVANT Valtoco (NRL-1) STAP-0011 XeriJect Diazepam EP-103 Zeneo Midazolam2 Generic Midazolam Diazepam Diazepam Alprazolam Diazepam Propofol Midazolam Administrati
Slide 18: Monitoring Devices: A Reasonable Precaution
Monitoring Devices: A Reasonable Precaution1-6 Supervision leads to decreased risk of sudden unexpected death in epilepsy (SUDEP)7Devices can help with early intervention when a convulsive seizure occursHaving a caretaker present during or immediately after a seizure is an advantageDevice technology
Slide 19: Conclusions
Conclusions Cluster seizures are common, especially in patients with frequent seizures, and are potentially harmfulRescue medication is effective but greatly underusedTreating early is beneficialMost patients should have a clear seizure action plan, preferably in writing and reviewed regularlyMany b
Slide 20: Healthy Volunteer Studies, Weight-Based Dosing and Patient PK
Allen H. Heller, MD, MPHFounder and CEO Pharma Study Design, LLCClinical Professor of Preventive MedicineKeck School of MedicineUniversity of Southern CaliforniaLos Angeles, California Healthy Volunteer Studies With Diazepam Buccal Film (DBF)Development of a Weight-Based Dosing Regimen Pharmacokinet
Slide 21: Healthy Volunteer Studies
Property of Aquestive Therapeutics, Inc. 21 Healthy Volunteer Studies Aquestive conducted a series of phase 1 studies using diazepam buccal film (DBF) and diazepam rectal gel (DRG) in healthy adultsDBF was dose-proportional—maximum plasma concentration (Cmax) increased in proportion to the dose—wher
Slide 22: DBF Exhibits Dose-Proportional Pharmacokinetics in Healthy Adults
DBF Exhibits Dose-Proportional Pharmacokinetics in Healthy Adults From Heller AH, et al. Presented at: Annual Meeting of the American Academy of Neurology; April 21-28, 2018; Los Angeles, CA; Neurology. 2018;90(15 suppl):P4.272. Mean Cmax Values by Diazepam Dose AUC0-t, area under the plasma concent
Slide 23: DRG Does Not Exhibit Dose-Proportional Pharmacokinetics
DRG Does Not Exhibit Dose-Proportional Pharmacokinetics Mean Cmax Values by Diazepam Dose Mean AUC0-t Values by Diazepam Dose DBF DBF From Heller AH, et al. Presented at: Annual Meeting of the American Academy of Neurology; April 21-28, 2018; Los Angeles, CA; Neurology. 2018;90(15 suppl):P4.273. AUC
Slide 24: Proposed Weight-Based Dosing Regimen for DBF
Proposed Weight-Based Dosing Regimen for DBF The weight-based dosing regimen for DBF was modeled to account for differences between DBF and DRG (linear pharmacokinetics and food effect associated with oral dosing)The proposed dosing regimen for DBF is designed such that, after a moderate-fat meal, t
Slide 25: More Reliable Absorption With DBF Than With DRG
DRG 20 mg (n=31) DRG 12.5 mg (n=32) DRG 5 mg (n=33) DBF 15 mg (n=33) More Reliable Absorption With DBF Than With DRG DBF produces peak plasma levels similar to DRG using lower doses In a comparative PK study in healthy adults,1 3 subjects exhibited extremely low diazepam concentrations after one or
Slide 26: Pharmacokinetics of DBF in Adult Patients Under Interictal and Ictal/Periictal Conditions
Pharmacokinetics of DBF in Adult Patients Under Interictal and Ictal/Periictal Conditions in Epilepsy Monitoring Unit An in-clinic study of patients with epilepsy compared diazepam exposure after a fixed 12.5-mg dose of DBF under an interictal condition (not during seizure) and an ictal/periictal co
Slide 27: Results: Mean Plasma Diazepam Concentration
Results Mean Plasma Diazepam Concentration After Administration of DBF Under Interictal and Ictal/Periictal Conditions: Fixed Dose vs Weight-Based Dosing (Simulated)1 Predicted plasma concentrations based on data from 21 patients with valid profiles for both interictal and ictal/periictal conditions
Slide 28: Conclusions: DBF Pharmacokinetics and Weight-Based Dosing Simulation
Conclusions: DBF Pharmacokinetics and Weight-Based Dosing Simulation DBF demonstrates a superior PK profile: linearity, bioavailability, reliabilityA weight-based dosing regimen was modeled from healthy volunteer studies adjusting for fed conditions; testing in adults with epilepsy confirmed that di
Slide 29: PK of DBF in Adult Patients With Epilepsy: Comparison With DRG
PK of DBF in Adult Patients With Epilepsy: Comparison With DRG Study Design and PatientsRandomized, multicenter, single-dose, open-label, 2-treatment, 2-sequence crossover study (NCT03953820)Adult patients on a stable regimen of antiseizure drugs randomized to receive a single dose of DBF and a sing
Slide 30: Pharmacokinetics of Diazepam Buccal Film: Comparison With Diazepam Rectal Gel
Pharmacokinetics of Diazepam Buccal Film in Adult Patients With Epilepsy: Comparison With Diazepam Rectal Gel Michael A. Rogawski, MD, PhD Professor of Neurology and PharmacologySchool of Medicine, University of California DavisDavis, California
Slide 31: Key Findings
Key Findings Geometric mean Cmax values after DBF were comparableCmax values for DBF significantly less variable than for DRG (P<0.0001)
Slide 32: Key Findings: Geometric Mean Cmax by Weight Groups
Key Findings Geometric Mean Cmax Stratified by Weight Groups (N=28) Geometric mean Cmax values were less variable with DBF than with DRG across patient weight categories Cmax, maximal plasma concentration; DBF, diazepam buccal film; DRG, diazepam rectal gel.aIncludes 4 patients with weight 112-124.5
Slide 33: Key Findings: PK Parameters After DBF and DRG
Key Findings Parameter DBF DRG Ratio of Geometric Means, DBF/DRG (%)a 90% CI (%) for Ratiob Cmax (ng/mL), geometric mean 204.26 211.22 96.70 70.53, 132.58 AUC0-t (ng•h/mL), geometric meanc 7290.40 5682.09 128.31 95.93, 171.61 AUC0-inf (ng•h/mL), geometric meanc 8672.09 6880.96 126.03 103.67, 153.21
Slide 34: Conclusions
Conclusions For patients with epilepsy after a moderate-fat meal, a single dose of DBF provides comparable overall exposure to diazepam to DRG with significantly less variability than DRG when each is administered according to its respective weight-based dosing regimenThese results confirm pharmacom
Slide 35: Safety and Tolerability of Chronic Intermittent Use of Diazepam Buccal Film
Safety and Tolerability Associated With Chronic Intermittent Use of Diazepam Buccal Film in Pediatric, Adolescent, and Adult Patients With Epilepsy Syndi Seinfeld, DO, MS Director of EpilepsyJoe DiMaggio Children’s Hospital Miami, Florida
Slide 36: Introduction and Objective
Introduction and Objective Cluster seizures and other bouts of more frequent or more severe seizures occur in many patients with epilepsy despite treatment with antiepileptic medications, and can lead to injury, hospitalization, status epilepticus, and risk of death1-3Available treatment options for
Slide 37: Administration and Dosing
Administration and DosingStudy participants were instructed to administer DBF for treatment of seizure episodes occurring in their home environments in which a benzodiazepine would ordinarily be administered for seizure rescueDBF was dispensed at weight- and age-based doses ranging from 5 to 17.5 mg
Slide 38: Results
Results As of May 31, 2019, 72 patients had enrolled, used DBF at least once Mean (SD) duration on study at interim analysis cutoff date was 192.0 (97.0) daysDBF dose administeredMean (SD): 8.7 (10.1) mgMedian (range): 5 (1-49) mg Characteristic Adults (n=59) Adolescents (n=7) Pediatric(n=6) Age, me
Slide 39: Results (cont'd): Adverse Events
Overall, 34 patients (47.2%) have reported 90 AEs7 treatment-related AEs occurred in 5 (6.9%) patients; all were mild in severity and resolved 13 serious AEs were reported by 9 (12.5%) patients; none were considered treatment-relatedNo patient discontinued study participation because of an AELocal b
Slide 40: Medication Administration
Medication Administration Of the 471 DBF exposures:At least 107 (22.7%) were self-administered by the patientThe majority (308 or 65.4%) occurred within 5 minutes of a seizureThere were no administration-related injuries in this study or over the almost 1000 exposures in the DBF program8 patients we
Slide 41: Results: DBF Usability
DBF usability data were reported by 64 patientsMean (SD) administrations per patient: 7.4 (7.7)All patients had first-attempt success at DBF administration on at least one use occasionAlmost all patients successfully administered DBF on first or second attempt (97.7%) Results Success Rates for DBF I
Slide 42: Results (cont'd): Reasons for Unsuccessful Placement
There were no cases of unsuccessful placement owing to swallowing of DBF before it adhered to buccal mucosa (Table)Patients and caregivers reported no difficulty opening the packaging in the majority of use occasions Patients and caregivers reported no difficulty removing DBF from inner packaging in
Slide 43: Conclusions
Conclusions In this observational study of chronic intermittent administration and use, DBF was found to be safe and well tolerated by pediatric, adolescent, and adult patients with epilepsy experiencing seizure emergencies Treatment-related AEs, including somnolence, were relatively uncommon after
Slide 44: Panel Discussion/Q&A
Panel Discussion/Q&A Gary Slatko, MDLawrence J. Hirsch, MDAllen H. Heller, MD, MPHMichael A. Rogawski, MD, PhDSyndi Seinfeld, DO, MS
Slide 45: Discussion for Panel
Discussion for Panel What would a medication like this—that’s easy to carry and could be quickly administered—mean for patients with epilepsy and caregivers?How does this buccal formulation compare with nasal formulations? Our data show a strong preference for oral formulations—what do your patients
Slide 46: Closing Remarks
Closing Remarks Keith Kendall President and Chief Executive Officer
Aquestive Therapeutics — Technical Presentation (December 2019) on 6ix