Slide 1: Vibrance-1 Alixorexton Phase 2 Study in Patients with Narcolepsy Type 1
Vibrance-1 Alixorexton Phase 2 Study in Patients with Narcolepsy Type 1 September 8, 2025 Exhibit 99.2
Slide 2: Forward-Looking Statements
Certain statements set forth in this presentation constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the potential therapeutic and commercial value of alixorexton (forme
Slide 3: Vibrance-1 Phase 2 Study of Alixorexton in Patients With Narcolepsy Type 1
Vibrance-1 Phase 2 Study of Alixorexton in Patients With Narcolepsy Type 1 Once-daily alixorexton demonstrated new, potential best-in-class features across a range of doses Compelling therapeutic benefit; statistically significant effect on excessive daytime sleepiness and significant improvements i
Slide 4: Today's Speakers
Today’s Speakers Marcus Yountz, M.D. Vice President, Clinical Development; Alixorexton Clinical Program Lead Giuseppe Plazzi, M.D., Ph.D. Vibrance-1 Lead Investigator; Director of the Narcolepsy Center at the IRCCS of the Neurological Sciences of Bologna; Professor of Childhood Neuropsychiatry, Univ
Slide 5: Vibrance-1 Examined the Effects of Alixorexton on Measures Relevant to Patients With NT1
Vibrance-1 Examined the Effects of Alixorexton on Measures Relevant to the Clinical Needs of Patients With NT1 BC-CCI = British Columbia Cognitive Complaints Inventory; BC-CCI-E = British Columbia Cognitive Complaints Inventory – Expanded; CGI-S = Clinical Global Impression of Severity; ESS = Epwort
Slide 6: Vibrance-1 Phase 2 Study: 6-Week Double-blind Period Followed by Open-label Extension
Vibrance-1 Phase 2 Study: 6-Week Double-blind Period Followed by an Open-label Extension Period With Dosing Flexibility Inclusion criteria Exclusion criteria aAll patients in the open-label extension period start with 6 mg alixorexton. Dose adjustment possible (up or down) during the first 2 weeks o
Slide 7: Primary Efficacy and Secondary Endpoints Were Evaluated at the End of the 6-week Period
Primary Efficacy and Secondary Endpoints Were Evaluated at the End of the 6-week Double-blind Treatment Period Weekly cataplexy rate at Week 6a Change in ESS from baseline to Week 6 Primary Endpoint Change in mean sleep latency on the MWT from baseline to Week 6 Key Secondary Endpoints z z TEAEs Vit
Slide 8: Vibrance-1 Phase 2 Study: Baseline Characteristics and Study Disposition
Vibrance-1 Phase 2 Study: Baseline Characteristics and Study Disposition Alixorexton once daily Placebo (N=23) 4 mg (N=23) 6 mg (N=22) 8 mg (N=24) Total (N=92) Disease Severity Mean Sleep Latency on MWT (minutes), Mean (SD) 2.8 (3.1) 3.3 (3.3) 3.4 (3.2) 2.8 (2.9) 3.1 (3.1) ESS, Mean (SD) 18.7 (2.7)
Slide 9: Primary Endpoint: Mean Sleep Latency on the MWT
Primary Endpoint: Mean Sleep Latency on the MWT Showed Alixorexton Achieved Normative Wakefulness at All Doses Primary Endpoint Analysis at Week 6 Alixorexton once daily Change from baseline at Week 6 (minutes)a PBO (N=23) 4 mg (N=23) 6 mg (N=22) 8 mg (N=24) LSM -0.6 21.6 23.5 25.5 (95% CI of LSM) (
Slide 10: MWT Results Highlight That Patients Differ in Physiological Response
MWT Results Highlight That Patients Differ in Physiological Response and Underscore Importance of Range of Doses Normative wakefulness (≥20 minutes1,2) achieved by ~75-80% of subjects across all cohorts ≥ 30-minute mean sleep latency achieved by majority of patients in 8 mg group 40-minute test maxi
Slide 11: Key Secondary Endpoint: Epworth Sleepiness Scale
Key Secondary Endpoint: Epworth Sleepiness Scale Showed Alixorexton Achieved Normative Wakefulness at All Doses aANCOVA model. Missing data were imputed using multiple imputation. 1. Johns MW, Sleep 1991; 14: 540-5. ANCOVA = analysis of covariance; CI = confidence interval; ESS = Epworth Sleepiness
Slide 12: Alixorexton Improved ESS Scores as Early as Week 2 and Sustained Through Week 13
Alixorexton Improved ESS Scores as Early as Week 2 and Sustained the Effect Through Week 13 aThis snapshot of the open-label extension reflects data as of 1 July 2025 from the 59 patients who had completed the Week 13 visit as of that date. Not all patients had completed the open-label extension at
Slide 13: Key Secondary Endpoint: WCR at Week 6
Key Secondary Endpoint: WCR at Week 6 Showed Alixorexton Reduced Cataplexy Events Versus Placebo Key Secondary Endpoint Analysis Alixorexton once daily WCR at Week 6a,c PBO (N=23) 4 mg (N=23) 6 mg (N=22) 8 mg (N=24) Mean incidence rate 13.1 6.4 4.0 8.4 (95% CI of incidence rate) (7.5, 22.9) (3.6, 11
Slide 14: Many Patients on Alixorexton Experienced No Cataplexy During Week 6
Many Patients on Alixorexton Experienced No Cataplexy During Week 6 = Alixorexton Achievement of 100% cataplexy reduction during Week 6a aThe minimum number of required cataplexy diaries was 5 days weekly. PBO = placebo.
Slide 15: Vibrance-1 Examined the Effects of Alixorexton on Measures Relevant to Patients With NT1
Vibrance-1 Examined the Effects of Alixorexton on Measures Relevant to the Clinical Needs of Patients With NT1 BC-CCI = British Columbia Cognitive Complaints Inventory; BC-CCI-E = British Columbia Cognitive Complaints Inventory – Expanded; CGI-S = Clinical Global Impression of Severity; ESS = Epwort
Slide 16: Narcolepsy Severity Scale for Clinical Trials (NSS-CT)
Narcolepsy Symptoms Excessive daytime sleepiness Cataplexy Hypnagogic/ hypnopompic hallucinations Sleep paralysis Narcolepsy Severity Scale for Clinical Trials (NSS-CT) Measures the Severity and Impact of the Core Symptoms of Narcolepsy 1. Dauvilliers Y, et al. Sleep 2020;43(6):1-11. 2. Dauvilliers
Slide 17: Alixorexton Significantly Improved Narcolepsy Symptom Severity in Patients With NT1
Alixorexton Significantly Improved Narcolepsy Symptom Severity in Patients With NT1 from Baseline to Week 6 aNSS-CT severity ratings: mild, 0-14; moderate, 15-28; severe, 29-42; very severe, 43-57. CI = confidence interval; LSM = least square means; NSS-CT = Narcolepsy Severity Scale-Clinical Trials
Slide 18: Most Patients on Alixorexton Reported Mild Narcolepsy Severity at Week 6
Most Patients on Alixorexton Reported Mild Narcolepsy Severity at Week 6 Alixorexton Baseline aValues shown within bars are rounded to the nearest whole number and may not sum to 100%. NSS-CT = Narcolepsy Severity Scale-Clinical Trials. Alixorexton Week 6
Slide 19: Fatigue Is a Persistent, Severe, and Debilitating Unmet Need in Narcolepsy
Fatigue Is a Persistent, Severe, and Debilitating Unmet Need That Impacts the Lives of Patients With Narcolepsy Most narcolepsy patients experience fatigue, which often persists even with treatment1-3 Fatigue negatively affects patients’ mental health, functional outcomes and overall quality of life
Slide 20: Alixorexton Significantly Reduced PROMIS-Fatigue Scores to Week 6
Alixorexton Significantly Reduced PROMIS-Fatigue Scores from Baseline to Week 6 in Patients With NT1 Baseline Week 2 Week 4 Week 6 CI = confidence interval; LSM = least square means; PBO = placebo; PROMIS = Patient Reported Outcomes Measurement Information System; SE = standard error. Upper Limit, N
Slide 21: Cognitive Impairment: BC-CCI Assesses Severity and Impact
Cognitive Impairment BC-CCI Assesses the Severity and Impact of Cognitive Impairment From the Patient’s Perspective BC-CCI = British Columbia Cognitive Complaints Inventory. Items include: Forgetfulness/memory problems Poor concentration Trouble expressing thoughts Trouble finding the right word Slo
Slide 22: Alixorexton Significantly Reduced Severity of Cognitive Impairment on the BC-CCI
Baseline Week 2 Week 4 Week 6 Alixorexton Significantly Reduced Severity of Cognitive Impairment on the BC-CCI From Baseline to Week 6 BC-CCI = British Columbia Cognitive Complaints Inventory; CI = confidence interval; LSM = least squares means; PBO = placebo; SD = standard deviation; SE = standard
Slide 23: Most Patients on Alixorexton Reported No or Minimal Cognitive Impairment at Week 6
Most Patients on Alixorexton Reported No or Minimal Cognitive Impairment on the BC-CCI at Week 6 Alixorexton Baseline Alixorexton Week 6 aValues shown within bars are rounded to the nearest whole number and may not sum to 100%. BC-CCI = British Columbia Cognitive Complaints Inventory.
Slide 24: Alixorexton Significantly Reduced the Impact of Cognitive Impairment
Alixorexton Significantly Reduced the Impact of Cognitive Impairment on NT1 Patients From Baseline to Week 6 Baseline Week 2 Week 4 Week 6 Change from baseline at Week 6 (Exploratory endpoint) Alixorexton once daily PBO (N=23) 4 mg (N=23) 6 mg (N=22) 8 mg (N=24) Baseline, mean (SD) 5.6 (2.5) 5.3 (2.
Slide 25: Patient-reported Outcome Measures Demonstrated Robustness and Consistency Across Doses
Patient-reported Outcome Measures Demonstrated Robustness and Consistency Across Doses and Assays Alixorexton is the first once-daily orexin 2 receptor agonist to demonstrate normalization of cognitive functioning and fatigue scores on patient-reported scales in addition to clinically meaningful imp
Slide 26: Alixorexton Was Generally Well Tolerated Over 6 Weeks of Treatment
Alixorexton was Generally Well Tolerated Over 6 Weeks of Treatment aIf a patient had multiple adverse events, the highest severity is presented in summary by severity, and the highest relationship to study drug is presented in summary by relationship. bRelationship of TEAE to the drug as determined
Slide 27: Majority of Insomnia and Blurred Vision Adverse Events Occurred Early and Resolved
Majority of Insomnia and Blurred Vision Adverse Events Occurred Early in Treatment and Resolved Within Days ≥ Insomnia Blurred Vision ≥ Data from six-week double-blind treatment period. If patient experienced more than 1 event, maximum duration is shown. No events of insomnia reported in placebo gro
Slide 28: Alixorexton Was Generally Well Tolerated Over 6 Weeks of Treatment
Alixorexton was Generally Well Tolerated Over 6 Weeks of Treatment Most TEAEs were mild to moderate in severity There were no serious TEAEs reported Most commonly reported TEAEs occurred within the 1st week of dosing Most insomnia events resolved within 1 week Most urinary events (pollakiuria and mi
Slide 29: Vibrance-1: Open-label Extension
Vibrance-1: Open-label Extension 4 mg Alixorexton 6 mg Alixorexton 8 mg Alixorexton Placebo 6-week Randomized Double-blind Treatment Period 6 0 Week 6 mg 4 mg Alixorexton 6 mg Alixorexton 8 mg Alixorexton 8 13 Optional 7-week Open-label Extension Dose Adjustment Opportunity All patients in the open-
Slide 30: Open-label Extension Dose Adjustment Provided Insight Into Patient Preference
Number of Patients Randomized Dose Group n = 23 n = 23 n = 22 n = 22 Open-label Extension Dose Adjustment Provided Insight Into Patient Preference *Ending dose preference. All patients in the open-label extension period start with 6 mg alixorexton. Dose adjustment possible (up or down) during the fi
Slide 31: Vibrance-1 Open-label Extension: Safety Summary
Vibrance-1 Open-label Extension: Safety Summary During the 7-week open-label extension (N=90): Alixorexton was generally well tolerated Most TEAEs were mild to moderate in severity There were no serious TEAEs reported For TEAEs most commonly reported in the double-blind period*, in the open-label ex
Slide 32: Vibrance-1 Lead Investigator Professor Giuseppe Plazzi
Vibrance-1 Lead Investigator Director of the Narcolepsy Center at the IRCCS of the Neurological Sciences of Bologna Professor of Childhood Neuropsychiatry, University of Modena and Reggio Emilia Professor Giuseppe Plazzi, M.D. Ph.D.
Slide 33: Conclusions
= Conclusions Once-daily alixorexton: Demonstrated statistically significant, clinically meaningful improvements on the MWT and ESS at Week 6 compared with placebo, achieving a normative wakefulness profile at all doses tested Improvements on the ESS were observed as early as Week 2 and sustained th
Slide 34: www.alkermes.com
www.alkermes.com