Epilepsy Treatment Update for Patients Suffering From Seizure Clusters - Tuesday, December 3, 2019 National Harbor, MD - amsus

 
Epilepsy Treatment Update for Patients Suffering From Seizure Clusters - Tuesday, December 3, 2019 National Harbor, MD - amsus
Epilepsy Treatment Update
for Patients Suffering
From Seizure Clusters

Tuesday, December 3, 2019
National Harbor, MD

                      US-P-NZ-SC-1900152 12/19
Epilepsy Treatment Update for Patients Suffering From Seizure Clusters - Tuesday, December 3, 2019 National Harbor, MD - amsus
!       Disclaimer

•       The speaker today is being compensated by UCB, the sponsor of this presentation
•       The use of products in any way other than that specified by the FDA approved US Prescribing
        Information is off-label and cannot be recommended by UCB
•       Disclosures: research grants from Lundbeck, Eisai; advisory boards and consulting for Abbot,
        Alliance, Aquestive, Eisai, Lundbeck, SK Life Sciences, UCB Pharma; speaker bureau for
        Aquestive, Eisai, Sunovion, UCB Pharma

                                                                                                  2
Epilepsy Treatment Update for Patients Suffering From Seizure Clusters - Tuesday, December 3, 2019 National Harbor, MD - amsus
What Is a Seizure Cluster?

  •          Seizure clusters can be broadly                                                                                         Various Alternative Names for Seizure Clusters5
             defined as acute episodes of
             consecutive seizures that occur with                                                                                                                                                         Acute
                                                                                                                                            Recurrent
                                                                                                                                                                              Flurries                   Repetitive
             short interictal periods and may be                                                                                            Seizures
                                                                                                                                                                                                         Seizures
             distinguishable from a patient’s typical
             seizure pattern or frequency1-4

  •          No consensus definition of seizure                                                                                              Cyclical                      Crescendo                      Serial
             clusters currently exists1                                                                                                      Seizures                       Seizures                     Seizures

Sources: 1. Haut SR. Curr Opin Neurol. 2015;28:143-150. 2. Mitchell WG. Epilepsia. 2996;37:S74-S80. 3. Haut SR. Epilepsy Behav. 2006;8:50-55. 4. Dreifuss FE, et al. N Engl J Med. 1998;338:1869-1875.                5
5. Jafarpour S, et al. Seizure. 2019;68:9-15.
Burden of Seizure Clusters

                                                     Impact of Seizure Clusters on Patients’ and Their Caregivers’ Lives
                                                                         Percent of Respondents, %

                                        Patients (N=259)                                                          Caregivers (N=263)
                                                Driving                                                                    Driving
                                                  69%

        Extracurricular                                                                        Extracurricular
                                                                     Overall mood                                                            Overall mood
          activities                                           69%                               activities
                               58%                                                                                                     55%
                                                                                                                  41%       10%

                               59%                                                                               52%                   48%
                                                               69%
                   Travel                                            Work                              Travel               34%              Work

                                                  67%
                                           Independence                                                                 Independence

                                          Seizure clusters represent substantial burdens to patients’ their caregivers’ lives
Source: Penovich PE, et al. Neurologist. 2017;22:207-214.                                                                                                   6
Gaps in Communication About Seizure Clusters

                                                             Healthcare Professional                                Community Member
                                              •      12-hour period for children                       •   Can range from daily to once a year
       Time frame
                                              •      24-hour period for adults
                                              •      Over a relatively short period of time, usually
       Duration                                                                                        •   Ranges from a few days to a few weeks
                                                     less than 24 hours
       Frequency                              •      Multiple seizures, usually 3 or more              •   No specific number of seizures

      Note: Based on qualitative reviews and analyses of the medical literature (Healthcare Professional) and of the Epilepsy Foundation
      website (Community Member). This theme refers to the understanding or the definition of seizure clusters as understood by healthcare professionals
      or epilepsy community members.

Source: Buelow JM, et al. Epilepsy Behav. 2016;57:16-22.                                                                                                   7
Average Seizure Cluster Duration
                        Compared With Isolated Seizures

       Seizure Duration Based on Position Within a Cluster Compared With Isolated (Non-Cluster) Seizuresa
                                                                    Mean (SD) Seizure Duration, Seconds   Intracluster vs Terminal
    Seizure Cluster                         Mean Number of
                                                                   Intracluster   Terminal     Isolated       Seizure Duration
      Definition                            Seizures/Cluster
                                                                     Seizures     Seizures     Seizures           P Valueb
2 or more seizures
                                                             2.8     71 (78)      84 (68)       90 (92)               0.014
  within 2 hours
2 or more seizures
                                                             3.2     78 (72)      95 (98)       86 (92)               0.011
  within 4 hours
2 or more seizures
                                                             3.8     82 (81)      83 (69)      91 (108)               0.294
  within 8 hours
a   Data based on EEG findings from 996 seizures among 92 patients.
b There   were no statistically significant differences between mean terminal seizure duration and mean isolated seizure duration.

Abbreviations: EEG, electroencephalogram.                                                                                            8
Source: Ferastraoaru V, et al. Epilepsia. 2016;57:889-895.
Seizure Clusters May Involve the Failure of
                        Inhibitory Mechanisms
                                                          Mechanisms Reported to Be Involved in Seizure Termination1

                                                Seizure onset zone
                                                                                                                    Substantia nigra pars reticulata

                 Single Neurons                                                       Local Network of Neurons                            Remote Brain Regions
Transmembrane ion gradients                                                     Gap junction decoupling                           GABAergic synaptic inhibition
Energy failure (eg, ATP or glucose loss)                                        Changes in neuromodulator levels
                                                                                GABAergic synaptic inhibition

                           Binding of benzodiazepines to the GABA receptor is believed to potentiate GABAergic inhibition 2
Abbreviations: ATP, adenosine triphosphate; GABA, γ-aminobutyric acid.                                                                                            9
Sources: 1. Lado FA, Moshé SL. Epilepsia. 2008;49:1651-1664. 2. Riss J, et al. Acta Neurol Scand. 2008;118:69-86.
Seizure Clusters and Hospitalizations

                                                Seizure-Related Hospitalizations Among Patients With Epilepsy (non-SE)
                                                                                        Patients, %
                                                      0%             25%                   50%              75%               100%

                      Seizure clustering
                                                                                                             73%
                           (N=41)

                                                                                                                    P=0.006

                             Nonclustering
                                                                                                      59%
                               (N=100)

                      Note: Seizure cluster defined as 3 or more seizures in 24-hour period.

Abbreviation: SE, status epilepticus.                                                                                                10
Source: Haut SR, et al. Epilepsia. 2005;46:146-149.
Seizure Clusters and Status Epilepticus

                                                              History of Convulsive Status Epilepticus Among Patients
                                                                          With and Without Seizure Clusters

                                                       100%                          Seizure clustering        Nonclustering

                                                       75%
                                         Patients, %

                                                                                            P=0.03                             P
Seizure Clusters and Mortality

                                             Survival With and Without Seizure Clusters
                                     100 –
Cumulative Proportion Surviving, %

                                      90 –
                                      80 –
                                      70 –                                                               Patients with seizure clusters have a
                                      60 –
                                                                                                         ~3.5-fold greater risk of death*
                                      50 –
                                      40 –                                                               compared to patients without clusters
                                      30 –
                                      20 –                                                               *95% CI, 1.25-9.78
                                               No Seizure Clusters (N=94)
                                      10 –     Seizure Clusters During Treatment (N=12)
                                       0–
                                         0    5      10         15        20    25   30   35   40   45
                                                      Years After Onset of Epilepsy

                     Abbreviation: CI, confidence interval.                                                                                      12
                     Source: Sillanpää M, Schmidt D. Brain. 2008;131:938-944.
Risk Factors for Experiencing Seizure Clusters
               Prevalence of Select Risk Factors Among Patients Aged 16 Years or Older With and Without Seizure Clusters

                                                                                               Patients With Risk Factor, %
                              Risk Factor
                                                        0%                               25%             50%              75%             100%
                     History of…
                                                                                                                          70.6%
                                Complex partial seizure                                                    48.5%
                                                                                                              51.0%
                                          Simple partial seizure                                       43.4%
                                                                                      15.4%
                                                 Status epilepticus          5.8%
                                                                                  10.5%
                                                   Febrile seizures            7.9%
                                                                                  10.5%
                                                 Nocturnal seizure            7.1%
                                                                                8.7%
                                                        Tonic seizure    2.0%
                                                                               7.8%
                                                        Drop seizure    1.9%
                                                                                                         Note: All P values
Seizure Emergency Action Plans
                                                                                                            Clinician Recommendations and Patient
    In a survey of 259 patients with epilepsy…
                                                                                                                 Responses to Seizure Clusters
                                                                                                                     -100%        -50%
                                                                                                                        Patients (N=259), % 0% Clinicians
                                                                                                                                                       50%(N=339),100%
                                                                                                                                                                   %
                                                                  30%
                                                                                                    Rescue medication              20%                          79%
                                                             Have a seizure
                                                             emergency plan                         Call doctor's office           20%                      67%

                                                                                                               Visit ER            24%                     61%

                                                                                                             Stay calm          34%                       50%

                                                                                           Extra/increased dose of AED                11%           28%

                                                                                                                  VNS                 10%          21%

                                                                                                      Visit urgent care                  7%     12%
              70%
         Do not have a                                                                                           Other                   5%   2%
     seizure emergency plan                                                                                                                               Patients
                                                                                                                                                          Patient
                                                                                                      Typically nothing           27%         1%          Physician
                                                                                                                                                          Clinicians

                                 Most patients with seizure clusters report that they do not have a seizure emergency plan
Abbreviations: AED, antiepileptic drug; ER, emergency room, VNS, vagus nerve stimulator.                                                                          14
Source: Penovich PE, et al. Neurologist. 2017;22:207-214.
Use of Various Benzodiazepines
                        as Rescue Medication
             Prescriptions for Rescue Medications Among                   Rescue Medication Use for Patients With Seizure Clusters (N=612)
                Patients With Seizure Clusters (N=612)
                                                        2.1%                            40%
                    10.8%
                                                   3+ prescriptions
                2 prescriptions
                                                                                        30%    28.9%

                                                                          Patients, %
                                                                                        20%

                                   30.6%
                               1 prescription                                           10%               7.8%
                                                            56.5%                                                    7.0%      6.9%
                                                                                                                                         5.4%
                                                        No prescription
                                                                                               n=177      n=48        n=43      n=42     n=33
                                                                                        0%
                                                                                              Lorazepam Diazepam    Diazepam Midazolam Clonazepam
                                                                                                 (oral)  (rectal)     (oral) (intranasal) (oral)

             Less than half (43.5%) of patients who experienced seizure clusters had a prescription for a rescue medication
Source: Chen B, et al. Epilepsy Res. 2017;133:98-102.                                                                                        15
Pharmacokinetics of Benzodiazepines

                                                                                         Tmax (hours)                                                 Elimination Half-lifea (hours)
                                0           1          2            3         4          5      6     7                      8   9   10   11     12
 Clorazepate (IM)                                                                                                                          2.7-11b
                                                                                                                                                                  >24
Clorazepate (PO)                                           0.5-2b
Clonazepam (PO)                                                                 1-4                                                                              19-60
   Clobazam (PO)                                      1.3-1.7                                                                                                    10-30
   Diazepam (PO)                                    0.5-1.5
   Diazepam (IM)                             0.5-1.0                                                                                                             21-70
    Diazepam (R)                          0.17-0.75
 Midazolam (PO)                              0.5-0.97
   Midazolam (IM)                      0.24-0.51                                                                                                                  1-4
                 c
   Midazolam (IN)                     0.15-0.32
 Lorazepam (PO)                                               2.4
  Lorazepam (SL)                                             2.3                                                                                                  7-26
  Lorazepam (IM)                                1.2
a Inhealthy subjects.
bT
   max for N-desmethyldiazepam after administration of clorazepate.
c Compounded intranasal midazolam.2

Abbreviations: IM, intramuscular; IN, intranasal; PO, oral; R, rectal; SL, sublingual.                                                                                                 16
Sources: 1. Riss J, et al. Acta Neurol Scand. 2008;118:69-86. 2. Knoester PD, et al. Br J Clin Pharmacol. 2002;53:501-507.
NAYZILAM® (midazolam) nasal spray, CIV
Product Overview
Please see Important Safety Information, including the Boxed Warning for concomitant use with opioids, included
in this presentation.

Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com

                                  NAYZILAM® is a registered trademark of the UCB Group of Companies.
                                  All other trademarks are the property of their respective owners.
                                  ©2019 UCB, Inc., Smyrna, GA 30080. All rights reserved.                         17
                                  US-P-NZ-SC-1900152 12/19
NAYZILAM® Is the First and Only Nasal Spray
                         Indicated to Treat Seizure Clusters
NAYZILAM is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent
seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in
patients with epilepsy 12 years of age and older.

                                                                         WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS
                                                                   Concomitant use of benzodiazepines and opioids may result in
                                                                   profound sedation, respiratory depression, coma, and death
                                                                   [see Warnings and Precautions (5.1), Drug Interactions (7.2)].
                                                                      Reserve concomitant prescribing of these drugs for use in patients
                                                                       for whom alternative treatment options are inadequate.
                                                                      Limit dosages and durations to the minimum required.
                                                                      Follow patients for signs and symptoms of respiratory depression
                                                                       and sedation.

                                                                   Please see additional Important Safety Information within this presentation.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.

                                                                                                                                                                            18
NAYZILAM® Is Now Available                                                                        Single-use nasal spray supplied in
                                                                                                                              boxes of 2 blister pack units

                  NAYZILAM is a midazolam formulation
                  designed for nasal delivery

                  NAYZILAM can be administered
                  by a non–healthcare professional
                                                                                                                                        Image is for illustrative
                                                                                                                                           purposes only.

                  NAYZILAM is contraindicated in patients with acute narrow-angle glaucoma. Concomitant use
                  of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation,
                  respiratory depression, coma, and death. NAYZILAM may cause increased CNS-depressant
                  effect when used with alcohol or other CNS depressants. Concomitant use with moderate or
                  strong CYP3A4 inhibitors may result in prolonged sedation due to a decrease in plasma
                  clearance of midazolam. Antiepileptic drugs, including NAYZILAM, increase the risk of suicidal
                  ideation and behavior. Midazolam is associated with a high incidence of partial or complete
                  impairment of recall for the next several hours.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   19
NAYZILAM Pharmacokinetics
       Key Pharmacokinetic Parameters                                                              Mean Plasma Concentration After 2 Doses of Intranasal Midazolam
              in Healthy Adults1                                                                      Administered 10 Minutes Apart in Patients With Epilepsy2,a,b

 Absorption
   • Median Tmax 17.3 minutes                                                                                                  Detected in plasma by 5 minutes post dose

                                                                                                  Mean (±SD) NAYZILAM Plasma
   • Mean absolute bioavailability ~44%

                                                                                                  Concentration (ng/mL)
 Distribution
   • Total volume of distribution ~226.5 L
   • ~97% protein bound
 Metabolism
   • Primarily liver and intestinal CYP3A4
 Elimination
                                                                                                                                                      Hours Post Dose
   • Half-life 2.1 hours to 6.2 hours

aMean   plasma concentration was estimated from the Pharmacokinetic Analysis Population: All subjects who received both test doses in the ARTEMIS I clinical trial, with
 sufficient plasma concentration data to accurately estimate pharmacokinetic parameters (n=235).2
bThe formulation of intranasal midazolam used in this study was different from the final formulation of NAYZILAM.
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc.

                                                                                Please see additional Important Safety Information within this presentation.
                                                                                Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   20
NAYZILAM® (midazolam) Nasal Spray, CIV
                         Important Safety Information
CONTRAINDICATIONS
NAYZILAM is contraindicated in patients with acute narrow-angle glaucoma.

RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation,
respiratory depression, coma, and death.
•         Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment
          options are inadequate.
•         Limit dosages and durations to the minimum required.
•         Follow patients for signs and symptoms of respiratory depression and sedation.

RISKS OF CARDIORESPIRATORY ADVERSE REACTIONS
Serious cardiorespiratory adverse reactions have occurred after administration of midazolam. Warn patients and
caregivers about the risks of respiratory depression, cardiac, and respiratory arrest.
Respiratory depression was observed with the administration of NAYZILAM during clinical trials. Cardiac or respiratory
arrest caused by NAYZILAM was not reported during clinical trials.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   21
NAYZILAM® (midazolam) Nasal Spray, CIV
                         Important Safety Information (cont’d)
CENTRAL NERVOUS SYSTEM DEPRESSION FROM CONCOMITANT USE WITH OTHER CENTRAL NERVOUS
SYSTEM DEPRESSANTS, OR MODERATE OR STRONG CYP3A4 INHIBITORS
Drug products containing midazolam, including NAYZILAM, have a central nervous system (CNS) depressant effect.

Risks from Concomitant Use with Other CNS Depressants
NAYZILAM may cause an increased CNS-depressant effect when used with alcohol or other CNS depressants
(eg, opioids). Warn patients and caregivers that the use of NAYZILAM in combination with alcohol or other CNS
depressant drugs may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may
contribute to profound and/or prolonged drug effect.

Risks from Concomitant Use with Moderate or Strong CYP3A4 Inhibitors
Concomitant use of NAYZILAM with moderate or strong CYP3A4 enzyme inhibitors may result in prolonged sedation
because of a decrease in plasma clearance of midazolam. Caution patients against engaging in hazardous
occupations requiring mental alertness, such as operating machinery, driving a motor vehicle or riding a bicycle until
they have completely returned to their level of baseline functioning.

Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   22
NAYZILAM® (midazolam) Nasal Spray, CIV
                         Important Safety Information (cont’d)
SUICIDAL BEHAVIOR AND IDEATION
Antiepileptic drugs (AEDs), including NAYZILAM, increase the risk of suicidal thoughts or behavior in patients taking
these drugs for any indication. Monitor patients treated with NAYZILAM for the emergence or worsening of
depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and
caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.

IMPAIRED COGNITIVE FUNCTION
Midazolam, including NAYZILAM, is associated with a high incidence of partial or complete impairment of recall for
several hours following an administered dose. Counsel patients on when they can engage in activities requiring
complete mental alertness, operate hazardous machinery, or drive a motor vehicle after taking NAYZILAM.

GLAUCOMA
Benzodiazepines, including NAYZILAM, can increase intraocular pressure in patients with glaucoma. NAYZILAM may
be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. NAYZILAM is
contraindicated in patients with narrow-angle glaucoma.

Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   23
NAYZILAM® (midazolam) Nasal Spray, CIV
                         Important Safety Information (cont’d)
ADVERSE REACTIONS
In the randomized, double-blind, placebo-controlled trial, the most common adverse reactions (≥5% in any NAYZILAM
treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.

NAYZILAM is a Schedule IV controlled substance.

Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   24
ARTEMIS I: NAYZILAM for the Acute Treatment
                          of Seizure Clusters in Patients ≥12 Years of Age1,2
                                                                     ARTEMIS I Study Design: Comparative Phase1,2

                                                                 1st                                                                                                           2nd
                                                                Dose                                                                                                          Dose

                                                     5 mg NAYZILAM
                                                      (double-blind)
                                                         n=134                                                   If seizure cluster did not
                                                                                                                   stop within 10 minutes
    Treatment
     Groups                                                                                                          Or another seizure                               5 mg NAYZILAM
  Randomized 2:1                                                                                                   occurred within 6 hours                              (open-label)
                                                          Placebo                                                     And no sign of
                                                       (double-blind)                                             respiratory depressiona
                                                           n=67

 •     Tolerability was assessed in the Test Phase in which 292 patients received two 5 mg doses of NAYZILAM separated by 10 minutes
       in the absence of a seizure: patients who met predefined criteria continued on to the Comparative Phase2
aThe   patient did not have
ARTEMIS I Efficacy Endpoints

                                      Primary Endpoint1                                                                      Key Secondary and Exploratory Endpoints1

                                                                                                                               Treatment success with second dose
                                          No recurrence of seizures                                                            (open‐label)
                                            within 6 hours of initial
                                           blinded study drug dose
                                                                                                                               Time to next seizure occurring
Treatment                                                                                                                      >10 minutes after drug administration
 Success                     =                                      +
                                                                                                                               Return to baseline functionality within
                                          Seizure termination within                                                           24 hours of drug administrationa
                                            10 minutes after initial
                                           blinded study drug dose

aReturn    to baseline functionality: time when subject was able to return to what he/she was doing prior to the seizure cluster.2
Sources: 1. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808. 2. Data on File. UCB Inc.

                                                                                  Please see additional Important Safety Information within this presentation.
                                                                                  Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   26
ARTEMIS I Baseline Characteristics
                          and Inclusion Criteria
Patient Population Size1                                                                                            Number of AEDs3
Safety Population: N=292
ARTEMIS I Baseline Characteristics:
                           Seizure Cluster History
                                      Seizure Characteristics                                                                                Cluster Seizure Typesa

                                                                                                                        Complex partial
                                                             NAYZILAM®             Placebo
                                                                                                                             Secondary
 Typical cluster duration (min)                                n=129                  n=63                                   generalized
    Median                                                      65.00                60.00                                 Simple partial
    Range                                                    2.5-4320.0           8.5-2880.0
                                                                                                                           Primary GTC
 Seizures per cluster episode                                  n=134                  n=67
    Median                                                      5.2                   6.0                                           Tonic
    Range                                                      2-200                 2-170
                                                                                                                                 Absence
 Episodes in year before visit                                 n=134                  n=67                                                                                     NAYZILAM 5 mg (n=134)
                                                                                                                               Myoclonic                                       Placebo (n=67)
    Median                                                       18                    15
    Range                                                      3-999                 4-600                                          Atonic
 Years since clusters onset                                    n=133                  n=63
                                                                                                                                    Other
    Median                                                       5.0                  5.0
    Range                                                     0.3-48.0             0.5-32.0                                                  0            20       40         60        80     100

                                                                                                                                                                    Percent of Patients, %
                                                                                                                                              aPatients   may have reported >1 seizure type.

             Patients enrolled in ARTEMIS I had several different seizure types, with a median cluster duration of 65 minutes
Abbreviation: GTC, generalized tonic-clonic.
Source: Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.

                                                                          Please see additional Important Safety Information within this presentation.
                                                                          Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.                28
More Than 50% of Patients Achieved
                                          Treatment Success With a Single Dose1
                                                                     Treatment Response With a Single Dose of NAYZILAM®1,2
                                    100                                                                                                                                                  NAYZILAM 5 mg
                                                    P=0.110
                                    90                                                                                                                                                   Placebo
                                    80
                                              81%                                                       P=0.007
              Percent of Patients

                                    70                                                                                                                 P=0.011
                                                              70%
                                    60
                                                                                                 58%
                                    50                                                                                                           54%
                                    40

                                    30                                                                        37%
                                                                                                                                                                 34%
                                    20

                                    10
                                             n=108            n=47                               n=78         n=25                              n=72           n=23
                                     0
                                           Seizure Termination                                   No Recurrence                                      Treatment
70% of Patients Achieved Treatment Success
                          With Any Dose2
                                     First Dose (blind)1,2                                       Second dose (open label)2,3
                                       5 mg NAYZILAM                                                  5 mg NAYZILAM

                                                   54%                                                                  55%
                                      Treatment Success
                                                 n=72/134
                                                                                                           Treatment Success
                                                                                                                       n=23/42
                                                                                                                                                                              70%
Randomized
 Treatment                           First dose (blind)1,2                                       Second dose (open label)2,3
  Groups                                   Placebo                                                    5 mg NAYZILAM
                                                                                                                                                             Overall Treatment Success2
                                                   34%                                                                  66%                                       in 122/175a patients
                                                                                                                                                                treated with NAYZILAM
                                       Treatment Success                                                   Treatment Success
                                                  n=23/67                                                              n=27/41

Respiratory depression was observed with the administration of NAYZILAM during clinical trials. Cardiac or respiratory
arrest caused by NAYZILAM was not reported during clinical trials.1
aOne   hundred seventy-five patients were treated with NAYZILAM: 134 patients in the NAYZILAM arm and 41 patients in the placebo arm.2
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc. 3. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.

                                                                                 Please see additional Important Safety Information within this presentation.
                                                                                 Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   30
NAYZILAM-treated Patients Had a Greater Probability
                          of No Seizure Recurrence for 24 Hours Post-dose
                                                          Probability of Experiencing No Seizures Over the 24‐hour Observation Period
                                                                        Beginning 10 Minutes After Drug Administration1,2
                             Probability of no Seizures

                                                                                                                                                                     NAYZILAM: 58%
                                                                                                                                                                                               21% difference
                                                                                                                                                                                               P=0.0124
                                                                                                                                                                      Placebo: 37%

                                                            NAYZILAM
                                                            Censored NAYZILAMa
                                                            Placebo
                                                            Censored Placeboa

                                                                          Time After Administration of Double-Blind Trial Drug (Hours)

Antiepileptic drugs (AEDs), including NAYZILAM, increase the risk of suicidal thoughts or behavior in patients taking these drugs
for any indication.1
aPatients
        who did not have another seizure before the end of the 24‐hour observation period, and who had not been administered the second dose of trial drug, were
 censored at the end of the observation period. Those administered the second dose of trial drug who did not have a seizure before the administration of the second
 dose were censored at the time of the second dose.2
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.

                                                                                 Please see additional Important Safety Information within this presentation.
                                                                                 Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.              31
With NAYZILAM®, More Patients Returned to Baseline
                                              Functionality Within 24 Hours vs Placebo
         Return to Baseline Functionality Within 24 Hours1                                                                                                 Median Time to Return to Full
                                        100
                                                                                                                                                             Baseline Functionality2,a
                                        90
                                        80
               Percent of Patients, %

                                        70
                                                  72.4
                                        60
                                                                                  29.1% difference
                                        50                                            P
NAYZILAM® Adverse Event Profile (≥ 2% of NAYZILAM
                          Patients and Greater Than Placebo)
                                                                                                                 NAYZILAMb
                                                                                                                                                                 • The most common adverse
       Body System/                                                                                 Placebo +                                   Any NAYZILAM       reactions (≥5% in any NAYZILAM
                                               Placebo                  NAYZILAM                                                  NAYZILAM
     Adverse Reactiona                                                                             NAYZILAM 5                                     Treatment        treatment group) were somnolence,
                                                                          5 mg                                                    5 mg + 5 mg                      headache, nasal discomfort, throat
                                                                                                       mg                                           Group
                                                                                                                                                                   irritation, and rhinorrhea1
                                                 N=26                        N=91                       N=41                        N=43           N=175
                                                  %                           %                          %                           %               %           • Most adverse reactions were mild
 Nervous System                                                                                                                                                    or moderate in intensity2
  Somnolence                                          4                        10                         10                 9                       10          • At least one adverse event related
  Headache                                            0                        7                          0                  2                       4             to acute central respiratory
  Dysarthria                                          0                        2                          2                  2                       2             depression was reported
 Application Site                                                                                                                                                  in 10 (3.4%) patients2
  Nasal Discomfort                                    8                         5                          7                 16                      9
  Throat Irritation                                   0                         2                          2                 7                       3           • NAYZILAM was well tolerated.
  Rhinorrhea                                          0                         3                          0                 5                       3
                                                                                                                                                                 • No patients discontinued during
  Product Taste Abnormal                              0                         4                          0                 0                       2
                                                                                                                                                                   the comparative phase
 Eye Disorders
                                                                                                                                                                   of the Phase 3 study of NAYZILAM2
  Lacrimation Increased                               0                         1                          2                 2                       2
aAdverse  reactions that occurred within 2 days after NAYZILAM administration are included. bPatients were permitted to take a second, open-label dose of NAYZILAM 5 mg
between 10 minutes and 6 hours following the initial blinded dose of NAYZILAM 5 mg or placebo if they experienced seizure recurrence or an incomplete resolution of the
episode. The Placebo + NAYZILAM 5 mg and NAYZILAM 5 mg + 5 mg columns represent patients who received a second dose of NAYZILAM 5 mg after receiving a
blinded initial dose of placebo or NAYZILAM 5 mg.
TEAE, treatment‐emergent adverse event.
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.

                                                                                Please see additional Important Safety Information within this presentation.
                                                                                Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.       33
NAYZILAM® Dosing
                                                                                                 Maximum Dosage &
                                       Dosing                                                   Treatment Frequency

    1st Dose           Administer one spray (5 mg)                                Do not use more than 2 doses
                       into one nostril                                           of NAYZILAM to treat a single episode

  2nd Dose Administer one spray (5 mg) into                                       Treat no more than 1 episode every
(if needed) opposite nostril after 10 minutesa                                    3 days or 5 episodes per month
                                                                                                                                                                   Image is for illustrative
                                                                                                                                                                      purposes only.

•     For patients at increased risk of respiratory depression from benzodiazepines, administration under healthcare professional
      supervision should be considered prior to treatment; this administration may be performed in the absence of a seizure episode.1
•     Benzodiazepines, including NAYZILAM, can increase intraocular pressure in patients with glaucoma. NAYZILAM may be used in
      patients with open-angle glaucoma only if they are receiving appropriate therapy. NAYZILAM is contraindicated in patients with
      narrow-angle glaucoma.1
•     Concomitant use of NAYZILAM with moderate or strong CYP3A4 enzyme inhibitors may result in prolonged sedation. 1
aIf
  the patient has not responded to the initial dose. Do not administer if the patient has trouble breathing or if there is excessive sedation uncharacteristic of the patient
during a seizure cluster episode.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.                 34
NAYZILAM® Treats Seizure Clusters
                         in the Outpatient Setting

                                          • Can be administered by any non–healthcare professional
                                          • No priming or assembly necessary

                                                • Can be administered in an outpatient setting

                                          • May be administered to a patient during or after a seizure within a cluster
                                          • Requires no active inhalation; patient may be unconscious

Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   35
Administering NAYZILAM®
 Prior to treatment, the healthcare professional should instruct the individual administering on how to identify seizure
 clusters and use the product appropriately

       1. HOLD                                                          2. PLACE                                                        3. PRESS
       Hold the nasal spray unit with                                   Place the tip of the nozzle into                                Press the plunger firmly.
       your thumb on the plunger and                                    one nostril until your fingers are
       your middle and index fingers on                                 against the bottom of the
       each side of the nozzle.                                         patient’s nose.
       Do not press the plunger yet.

Please see the full instructions for use in the Prescribing Information and discuss with the patient and their caregiver.
Source: NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc.

                                                                   Please see additional Important Safety Information within this presentation.
                                                                   Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.   36
NAYZILAM® for the Treatment of Seizure Clusters
       10 MINUTES TO STOP SEIZURE CLUSTERS1                                                                                         90 MINUTES TO GET PATIENTS BACK TO BASELINE FUNCTION2
       • In 81% of patients, NAYZILAM terminated seizure cluster activity                                                           • For all seizure clusters treated with NAYZILAM,
          within 10 minutesa,b                                                                                                         the median time to return to full baseline functionalityc after trial drug
                                                                                                                                       administration was ~90 minutes2,d
       No seizure recurrence for up to 6 hours1
                                                                                                                                    • Midazolam, including NAYZILAM, is associated with a high incidence
       • 58% of patients had no seizure recurrence between
                                                                                                                                       of partial or complete impairment of recall for several hours following
          10 minutes and up to 6 hours after drug administrationa
                                                                                                                                       an administered dose.1
       Treatment Success
       • First dose 54%1                                                                                                            24 HOURS OF NO SEIZURE RECURRENCE
       • All doses 70%2                                                                                                             IN MAJORITY OF PATIENTS1
       • Serious cardiorespiratory adverse reactions have occurred after                                                            • Treatment with NAYZILAM significantly prolonged the time
          administration of midazolam. Warn patients and caregivers about                                                              to the next seizure within 24 hours after double-blind study drug
          the risks of respiratory depression, cardiac and respiratory arrest. 1                                                       administration compared with placebo (P=0.012).3
       • Respiratory depression was observed with the administration of                                                             • In the randomized, double-blind, placebo-controlled trial,
          NAYZILAM during clinical trials. Cardiac or respiratory arrest                                                               the most common adverse reactions (≥5% in any NAYZILAM
          caused by NAYZILAM was not reported during clinical trials.1                                                                 treatment group) were somnolence, headache, nasal discomfort,
                                                                                                                                       throat irritation, and rhinorrhea.1
Important Safety Information1
RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation, respiratory depression, coma, and death.
• Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.
aBaseline duration of seizure clusters in NAYZILAM arm was a median of 65 minutes (2.5-4320.0 minutes).3 bPrimary endpoint of treatment success included 2 components: the
 termination of seizures within 10 minutes after the double-blind (first) dose and no recurrence of seizures between 10 minutes and 6 hours (double-blind observation period).1
 CExploratory endpoint: time to return to full baseline functionality as determined by the caregiver. 3 dRange: 1.1-2.0 hours.2
Sources: 1. NAYZILAM [prescribing information]. Smyrna, GA: UCB Inc. 2. Data on file. UCB Inc. 3. Detyniecki K, et al. Epilepsia. 2019;60:1797-1808.

                                                                                 Please see additional Important Safety Information within this presentation.
                                                                                 Please refer to full Prescribing Information provided by the UCB Representative and visit www.NAYZILAM.com.                37
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