Slide 1: Alkermes Oral Presentation Presented at SLEEP 2026
ALKERMES ORAL PRESENTATION PRESENTED AT SLEEP 2026 JUNE 17, 2026 Table of Contents Vibrance-2: A Randomized Phase 2 Study Evaluating Efficacy and Safety of the Orexin 2 Receptor Agonist Alixorexton in Patients with Narcolepsy Type 2 Important Information About This Document This document includes sc
Slide 2: Vibrance-2: A Randomized Phase 2 Study of Alixorexton in Narcolepsy Type 2
Vibrance-2: A Randomized Phase 2 Study Evaluating Efficacy and Safety of the Orexin 2 Receptor Agonist Alixorexton in Patients With Narcolepsy Type 2 Richard K. Bogan,1 Giuseppe Plazzi,2,3 Emmanuel Mignot,4 Rafael del Río Villegas,5,6 Bruce Corser,7 Brendon J. Yee,8 Diego García-Borreguero,9 Chad Ru
Slide 3: Author Financial Disclosures
Ineligible companies are those whose primary business is producing, marketing, selling, re-selling, or distributing health care products used by, or on patients. No, I HAVE NOT had a financial relationship with an ineligible company in the past 24 months. Yes, I HAVE had a financial relationship wit
Slide 4: Orexin System: Master Regulator of the Sleep/Wake Cycle
Orexin System: Master Regulator of the Sleep/Wake Cycle • The orexin system initiates and regulates the cascade of neurologic interactions that stabilize the sleep/wake cycle and modulate diverse neuronal functions beyond wakefulness, such as fatigue, cognition, and mood1-3 • The OX2R is the main re
Slide 5: Orexin 2 Receptor Agonism with Alixorexton
Orexin 2 Receptor Agonism with Alixorexton • Alixorexton is a highly potent and selective OX2R agonist that has demonstrated robust wake stabilization in patients with NT1 in a phase 2 study • Alixorexton also demonstrated improvements in cognitive impairment and fatigue in this population • A phase
Slide 6: Vibrance-2 Phase 2 Study: 8-Week Double-Blind Period Followed by Open-Label Extension
Vibrance-2 Phase 2 Study: An 8-Week Double-Blind Period Followed by an Open-Label Extension With Dosing Flexibility Inclusion criteria • Participants with NT2 (ICSD-3-TR) with residual EDS • ESS ≥ 12 during screening period • Age 18 to ≤ 70 years • BMI ≥ 18 and ≤ 40 kg/m2 8-Week RDBT Period Safety •
Slide 7: Dual Primary Efficacy and Other Endpoints Were Evaluated at Week 8
Dual Primary Efficacy and Other Endpoints Were Evaluated at Week 8 Dual primary endpoints Inclusion criteria Change in mean sleep • Participants with NT2 (ICSD-3-TR) latency on the MWTa from with residual EDS baseline to week 8 • ESS ≥ 12 during screening period • Age 18 to ≤ 70 years zz Change in E
Slide 8: Baseline Demographic and Disease Characteristics
Baseline Demographic and Disease Characteristics RDBT assignment at baselinea Overall Alixorexton Demographics Placebo 10 mg 14 mg 18 mg Total 33.8 years Age (n = 24) (n = 23) (n = 22) (n = 24) (N = 93) (mean) Disease severity Female Mean sleep latency on Sex 6.0 (4.1) 5.3 (3.4) 5.5 (3.7) 5.7 (4.6)
Slide 9: Mean Sleep Latency on the MWT Showed Improved Wakefulness at Week 8
Mean Sleep Latency on the MWT Showed Alixorexton Improved Wakefulness at Week 8 20 Primary endpoint analysis at week 8 Mean sleep latency on MWT Alixorexton 15 16.1 Change from Mean (SE), minutes 13.7 13.9 baseline PBO 10 mg 14 mg 18 mg at week 8 (minutes)a (n = 24) (n = 23) (n = 22) (n = 24) 10 LSM
Slide 10: Clinically Meaningful Improvements in ESS as Early as Week 2
Clinically Meaningful Improvements With Alixorexton Were Observed in ESS as Early as Week 2 and the Effect was Maintained Through Week 8 RDBT Period Primary endpoint analysis at week 8 20 Change Alixorexton from baseline PBO 10 mg 14 mg 18 mg at week 8a (n = 24) (n = 23) (n = 22) (n = 24) ESS score
Slide 11: Mean ESS Scores Continued to Improve in the Open-Label Extension
Mean ESS Scores Continued to Improve in the Open-Label Extension Through Week 13 RDBT Period OLE Period 20 All patients started with alixorexton 14 mga,b 2-week Fixed dose dose period ESS score adjustment 15 Mean (SE) period Upper limit of normative ESS1 10 PBO 10 mg 14 mg Alixorexton 18 mg 5 Baseli
Slide 12: Majority Reported Normal or Mild EDS at Week 8
The Majority of Participants Receiving Alixorexton Reported Normal or Mild EDS at Week 8 with Continued Improvement Through Week 13 Baseline Week 8 Week 13: Open -Label Alixorexton a,b 100 4 5 71 78 86 67 39 38 18 21 18 10 5 ESS category, no. (%) 17 5 10 80 4 6 10 23 4 81 4 18 75 75 71 60 10 22 14 5
Slide 13: PROMIS-Fatigue: Scores Improved Through Week 13
PROMIS-Fatigue: Scores Improved as Early as Week 2 and Continued to Improve Through Week 13, With Mean Values in the Normal Range RDBT Period OLE Period 70 PROMIS-Fatigue score All patients started with alixorexton 14 mga,b 2-week Fixed dose Change Alixorexton dose period from adjustment baseline 10
Slide 14: BC-CCI: Improvements in Severity of Cognitive Impairment
BC-CCI: Clinically Meaningful Improvements in Severity of Cognitive Impairment Were Observed as Early as Week 2, with Continued Improvement Through Week 13 RDBT Period OLE Period 12 All patients started with alixorexton 14 mga,b 10 2-week Fixed dose Change Alixorexton dose period from baseline BC-CC
Slide 15: Alixorexton Generally Well Tolerated in Double-Blind and Open-Label Periods
Alixorexton was Generally Well Tolerated During 8 Weeks of Double-Blind Treatment and in the Open-Label Period RDBT Period Alixorexton Through 8 weeks of double- Placebo 10 mg 14 mg 18 mg blind treatment and 5 weeks of n (%) (n = 24) (n = 23) (n = 22) (n = 24) open-label treatment: Any TEAEa 16 (67)
Slide 16: Alixorexton Generally Well Tolerated in Double-Blind and Open-Label Periods (Detail)
Alixorexton was Generally Well Tolerated During 8 Weeks of Double-Blind Treatment and in the Open-Label Period RDBT Period Open-label Alixorextonb Alixorexton RDBT Assignment at Baselinec Placebo 10 mg 14 mg 18 mg Placebo 10 mg 14 mg 18 mg n (%) (n = 24) (n = 23) (n = 22) (n = 24) (n = 24) (n = 20)
Slide 17: Alixorexton is the First OX2R Agonist to Show Clinically Meaningful Improvements in NT2
Alixorexton is the First OX2R Agonist to Show Clinically Meaningful Improvements in Wakefulness, EDS, Cognition and Fatigue in Participants with NT2 • Alixorexton demonstrated clinically meaningful improvements at Week 8 in: • Wakefulness on the MWT • Daytime sleepiness on the ESS • Fatigue on the P
Slide 18: Alixorexton is Being Evaluated in NT1, NT2, and IH
Alixorexton is Being Evaluated in NT1, NT2, and IH1-7 NT1 Once-daily dosing Complete Phase 2 NT2 Once-daily dosing Complete IH Once-daily and split dosing Recruiting Study 301 Open-label Study Recruiting (up to 5 years) NT1 Once-daily and split dosing Phase 3 Recruiting NT2 Once-daily and split dosi
Slide 19: Acknowledgments
Acknowledgments The authors would like to thank: The participants Their families and caregivers Vibrance-2 investigators and their staff Funding provided by Alkermes SLEEP 2026 | June 14 – 17, 2026 18