Alkermes (ALKS) Status Update summary

Program and Clinical Development Overview

• ALKS-2680 is a potent, selective, once-daily oral orexin-2 receptor agonist advancing through phase 2 trials for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), targeting both orexin-deficient and non-deficient hypersomnolence disorders.

• Phase 1b data showed statistically significant, clinically meaningful, dose-dependent improvements in wakefulness, sleep latency, and alertness across NT1, NT2, and IH, with a favorable safety and tolerability profile.

• Phase 2 studies (Vibrance-1 for NT1 and Vibrance-2 for NT2) are ongoing, using randomized, placebo-controlled, parallel-group designs with open-label extensions; a phase 2 study in IH (Vibrance-3) is planned.

• Dose selection and trial design are informed by robust preclinical and translational modeling, integrating pharmacokinetics, pharmacodynamics, and patient-specific data.

• ALKS-2680 is currently the only OX2R agonist in phase 2 development for both narcolepsy subtypes.

Key Phase 1b Study Findings

• In NT1, single doses of 1, 3, and 8 mg led to significant, dose-dependent increases in mean sleep latency (up to 34 minutes placebo-corrected at 8 mg) and improved alertness, supporting once-daily dosing.

• In NT2, single doses of 5, 12, and 25 mg produced significant, dose-dependent increases in mean sleep latency, with higher doses exceeding healthy controls' averages, and improved alertness.

• In IH, single doses of 5, 12, and 25 mg resulted in significant, dose-dependent improvements in sleep latency and alertness, with higher doses exceeding healthy controls' mean sleep latency.

• Across all studies, adverse events were mostly mild and transient, with no serious or severe events and no cardiovascular safety signals.

• Most common side effects included insomnia, polyuria, and dizziness; visual disturbances and urinary urgency were rare, mild, and transient.

Phase 2 Study Designs and Objectives

• Vibrance-1 (NT1): Randomized, double-blind, placebo-controlled, parallel-group study of 4, 6, or 8 mg once daily for 6 weeks, followed by open-label extension; primary endpoint is change in mean sleep latency.

• Vibrance-2 (NT2): Randomized, double-blind, placebo-controlled, parallel-group study of 10, 14, or 18 mg once daily for 8 weeks, followed by open-label extension; primary endpoint is change in mean sleep latency.

• Both studies include secondary endpoints such as changes in Epworth Sleepiness Scale, cataplexy rate (NT1), safety, and exploratory patient- and clinician-reported outcomes.

• Enrollment targets approximately 80 patients per study, with sites in the US, Australia, and Europe.

• The program is structured to support rapid progression to phase 3, with data readouts expected in the second half of next year.