Slide 1: A Novel Investigational Treatment for Hypersomnia: Where We Are and Where We Need to Go
A Novel Investigational Treatment for Hypersomnia: Where We Are and Where We Need to Go Christopher L. Drake PhD, FAASM Professor of Medicine Michigan State College of Human Medicine Director of Sleep Research, Henry Ford Health June 1, 2024 © 2024 Zevra Therapeutics, Inc. 1 MRC- 2400031 05/24
Slide 2: Zevra Is Committed to Rare Diseases
Zevra Is Committed to Rare Diseases Zevra’s Approach Zevra is a patient-centric organization dedicated to developing transformational therapies for rare diseases with limited or no treatment options. Our Mission Employ creative, outside-the-box strategies to overcome drug development and regulatory
Slide 3: PWIH Experience Multiple Symptoms With Excessive Daytime Sleepiness Being Universal
PWIH Experience Multiple Symptoms With Excessive Daytime Sleepiness (EDS) Being Universal Responses from 10 persons with idiopathic hypersomnia (PWIH) in an advisory board survey What are your primary symptoms of IH? 100% 90% Percentage of Participants 80% 70% 60% 50% 100% 40% 80% 70% 70% 30% 60% 20
Slide 4: Primary Symptoms of IH Remain Despite Current Treatments
Primary Symptoms of IH Remain Despite Current Treatments Responses from 10 persons with idiopathic hypersomnia in an advisory board survey Despite treatment, please select the symptoms which are still most prominent. 100% 90% Percentage of Participants 80% 70% 60% 50% 40% 80% 80% 70% 30% 50% 50% 20%
Slide 5: Review of Zevra's Investigational Treatment for IH
Review of Zevra’s Investigational Treatment for IH 5
Slide 6: Serdexmethylphenidate (SDX), a Pro-Drug of d-Methylphenidate
Serdexmethylphenidate (SDX), a Pro-Drug of d-Methylphenidate Approved Drug Ligand Pro-Drug with Potentially Cleaved Drug through Human Improved Attributes Metabolic Process Serdexmethylphenidate (SDX) is a Pro-Drug of d-Methylphenidate Active Drug: d-methylphenidate Ligand: Carboxymethylene linker +
Slide 7: Predicted d-MPH Plasma Levels in Individuals at Steady-State Dosing
Predicted d-MPH Plasma Levels in Individuals at Steady-State Dosing Day Night BID = Twice per day (half daily dose 2x/day) (1x at night (bedtime)/ 1x in morning) QD = Once per day (daily dose at night) (1 x at night/bedtime) 8AM 10AM Noon 2PM 4PM 6PM 8PM 10PM 12AM 2AM 4AM 6AM 8AM Time BID: Morning D
Slide 8: KP1077 Phase 2 Trial Design in People With IH
KP1077 Phase 2 Trial Design in People With IH Open-Label Double-Blind Screening Period Titration Period Withdrawal ≤35 days 5 weeks Period 2 weeks KP1077 KP1077 Placebo V1 V1A V2 V3 V4 V5 V6 V7 V8 FU Screening Visit LD ↑ ↑↓ ↑↓ ↑↓ 1 week Titration Window V = Visit; FU = Follow-Up Phone Call; LD = Low
Slide 9: Most Adverse Events Observed With KP1077 Were Mild and Resolved Quickly
Most Adverse Events (AEs) Observed With KP1077 Were Mild and Resolved Quickly Insomnia was the most frequent AE • Most frequent AEs (>5%): insomnia (24%), headache (9%), anxiety (6%), nausea (6%), and decreased appetite (6%) • Approximately same incidence and similar types of AEs in each dosing regi
Slide 10: Many of the Reported Symptoms of IH Were Evaluated in the Phase 2 Trial
Many of the Reported Symptoms of IH Were Evaluated in the Phase 2 Trial Primary and secondary endpoints were patient-reported evaluations • Excessive daytime sleepiness (EDS) as measured by the Epworth Sleepiness Scale (ESS) • Sleep inertia as measured by the Sleep Inertia Visual Analog Scale (SIVAS
Slide 11: Results Showed a Reduction in Daytime Sleepiness
Phase 2 Trial Results Showed a Reduction in Daytime Sleepiness Study participants reported less daytime sleepiness throughout the 7-week trial Open-Label Double-Blind Severe Titration Period Period Less Daytime Sleepiness Moderate Mild Not Pathological 11 ClinicalTrials.gov Identifier NCT05668754. A
Slide 12: Results Showed a Reduction in Sleep Inertia
Phase 2 Trial Results Showed a Reduction in Sleep Inertia Study participants reported that it was easier to wake up in the morning Open-Label Double-Blind Titration Period Period Less Sleep Inertia 12 ClinicalTrials.gov Identifier NCT05668754. Available at: https://clinicaltrials.gov/study/NCT056687
Slide 13: The Idiopathic Hypersomnia Severity Scale Measures Both IH Symptoms and Impaired Function
The Idiopathic Hypersomnia Severity Scale Measure Both IH symptoms and Impaired Function The IHSS is a patient-reported questionnaire • The IHSS measures severity of both nighttime and daytime IH symptoms • The IHSS measures impaired daytime functioning • Patients rate a severity and frequency on 17
Slide 14: Results Showed a Reduction in the Severity of IH Symptoms and Impaired Function
Phase 2 Trial Results Showed a Reduction in the Severity of IH Symptoms and Impaired Function Open-Label Double-Blind Severe Titration Period Period Less IH Severity Moderate Mild Not Pathological 14 ClinicalTrials.gov Identifier NCT05668754. Available at: https://clinicaltrials.gov/study/NCT0566875
Slide 15: Brain Fog Scale
Brain Fog Scale Exploratory Scale: Not validated in IH Total Score: • Range: 0-76 • Higher score = more symptoms/more severe symptoms • Neutral = 38 15 ClinicalTrials.gov Identifier NCT05668754. Available at: https://clinicaltrials.gov/study/NCT05668754?intr=serdexmethylphenidate&rank=2
Slide 16: Results Showed a Reduction in Brain Fog Symptoms
Phase 2 Trial Results Showed a Reduction in Brain Fog Symptoms Captures patient-reported answers to 19 questions, rating the symptoms of brain fog Open-Label Double-Blind Titration Period Period Less Brain Fog 16 ClinicalTrials.gov Identifier NCT05668754. Available at: https://clinicaltrials.gov/stu
Slide 17: Conclusions from the Phase 2 Trial
Conclusions from the Phase 2 Trial • KP1077 was well tolerated in people with IH, after either once-per-day or twice-per- day dosing • Meaningful improvements in daytime sleepiness, sleep inertia, and brain fog were reported by the trial participants for both dosing regimens • Results provided valua
Slide 18: Questions and Answers Thank you!
Questions and Answers Thank you! 18