Eisai (4523) investor relations material

Scientific and clinical background

• E2086 is a selective orexin receptor 2 agonist developed to address orexin deficiency, the underlying cause of narcolepsy type 1 (NT1), by promoting wakefulness and mitigating cataplexy symptoms in preclinical models.

• The compound was discovered through high-throughput screening and features a complex, unique chemical structure, with significant improvements in activity achieved through medicinal chemistry and AI-based screening.

• E2086 is positioned as a once-daily therapy, leveraging expertise in both orexin antagonists and agonists, aiming for broad application in sleep disorders.

• Preclinical studies showed E2086 has strong efficacy and safety in non-clinical models.

• Narcolepsy type 1 is characterized by orexin deficiency, leading to high disease burden and unmet medical needs.

Phase 1b clinical trial design and methodology

• The Phase 1b trial was a multicenter, randomized, double-blind, five-period crossover study in adults with NT1, comparing three doses of E2086 (5, 10, 25 mg), placebo, and modafinil.

• Each participant received all treatments in a randomized sequence, with washout periods between doses, and efficacy was assessed using the Maintenance of Wakefulness Test (MWT) and Karolinska Sleepiness Scale (KSS).

• 21 participants (mean age 35.6 years, 42.9% female) were included in the safety analysis; 19 completed all treatments.

Efficacy results

• E2086 at all tested doses significantly extended sleep latency compared to placebo, with 10 and 25 mg doses outperforming modafinil in maintaining wakefulness up to seven hours post-dose.

• Subjective sleepiness scores (KSS) also improved significantly with E2086, especially at 10 and 25 mg, which showed greater efficacy than modafinil.

• E2086 10 mg and 25 mg sustained wakefulness for at least 30 minutes in each MWT trial.

• All doses of E2086 resulted in statistically significant longer sleep latencies versus placebo (P < 0.0001) and modafinil.

• At higher doses, patients achieved or exceeded normal wakefulness levels seen in healthy subjects, with sustained effects observed throughout the day.