Alkermes (ALKS) Status Update summary

Program overview and clinical progress

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

• Phase 1b data showed ALKS-2680 is generally safe, well-tolerated, and demonstrated statistically significant, clinically meaningful, dose-dependent improvements in wakefulness, sleep latency, and alertness across all indications.

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

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

• The program is built on robust preclinical and translational modeling, enabling precise dose selection and rapid progression to later-stage development.

Key phase 1b study findings

• In NT1, single doses of 1, 3, and 8 mg ALKS-2680 led to significant, dose-dependent increases in mean sleep latency (up to 34 minutes placebo-corrected at 8 mg) and improved alertness.

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

• Safety and efficacy support once-daily dosing for all indications.

Unmet needs and patient insights

• Narcolepsy and IH patients face significant diagnostic delays, with only about 50% of narcolepsy cases diagnosed and an average 10–15 year lag from symptom onset to diagnosis.

• Current therapies yield only moderate satisfaction among physicians and even lower satisfaction among patients, with persistent symptoms and major impacts on daily life, mental health, and relationships.

• Patients express a strong desire for better symptom control, non-stimulant, disease-modifying therapies, and improved quality of wakefulness, cognition, and fatigue.

• Stigma, lack of awareness, and limited access to knowledgeable providers further exacerbate challenges for patients.