A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ORX750 in Subjects With Narcolepsy and Idiopathic Hypersomnia (CRYSTAL-1)

Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) are rare conditions that make people feel very sleepy during the day (often referred to as excessive daytime sleepiness [EDS]). People living with these conditions might find it hard to stay alert and pay attention when they are at school, working, driving, or performing other daily activities.

While all conditions result in feeling sleepy, there are some differences in other common symptoms:

• NT1: People with NT1 often feel very tired during the day and experience cataplexy. Cataplexy is a sudden loss of muscle strength, which can cause someone to collapse or lose control of their muscles for a short time. This is often triggered by strong emotions, such as laughter or surprise. They may also have trouble sleeping well at night.
• NT2: People with NT2 feel sleepy during the day, just like NT1, but they do not have cataplexy.
• IH: People with IH feel tired during the day, even after sleeping a lot at night. They may sleep for long periods, take long naps, and find it hard to wake up.

Orexin is a protein in the brain that helps coordinate a system that plays an important role in helping people to stay awake during the daytime. Cleminorexton (also known as ORX750) is designed to mimic the action of orexin. The purpose of this study is to see how safe and tolerable ORX750 is in NT1, NT2, and IH, and learn about what the drug does to the body. Another goal of the study is to see if ORX750 can help people with NT1, NT2, and IH feel less sleepy and make other symptoms better.

Inclusion Criteria:

• 18-65 years of age
• BMI ≥17 and ≤37 kg/m2
• Meets the diagnostic criteria of Narcolepsy Type 1 (NT1), Type 2 (NT2) or Idiopathic Hypersomnia (IH) according to ICSD-3-TR criteria
• Is willing and able to discontinue all medications used for the treatment of narcolepsy or idiopathic hypersomnia
• Is willing and able to adhere to additional protocol requirements

Exclusion Criteria:

• A medical disorder other than NT1, NT2, or IH that is associated with excessive daytime sleepiness (EDS).
• Presence of significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematological, malignancy, endocrine, neurological or psychiatric disease