Analysts at BMO Capital Markets said Centessa’s orexin receptor agonist has “best-in-class” potential for narcolepsy, putting the company in a strong position in the $15 billion market.
Centessa Pharmaceuticals’ investigational orexin receptor agonist ORX750 promotes wakefulness in sleep-deprived healthy volunteers, pointing to its potential as a treatment for narcolepsy and other sleep disorders, according to a Phase I readout on Saturday.
In a note to investors, analysts at Leerink Partners called ORX750’s signals of efficacy “compelling,” pointing to its “significant improvements in mean sleep latency … and subjective alertness” compared to placebo. This readout, according to Leerink, “reinforces ORX750 as a potentially best-in-class OX2R agonist relative to competitors.”
Centessa’s data, presented at the 2025 Annual Meeting of the American Academy of Neurology over the weekend, showed that patients treated with 5 mg of ORX750, taken orally, had mean sleep latency, a measurement of how long it takes a patient to fall asleep, of 37.9 minutes, whereas sleep was delayed by an average of 15.3 minutes in placebo comparators. The treatment difference of 22.6 minutes was highly statistically significant, according to Centessa’s presentation.
Patients on ORX750 were likewise significantly more alert during the day than those on placebo, measured at least three hours after dosing.
ORX750 also had a largely clean safety profile, with treatment-emergent adverse events being mild or moderate in severity. Side effects were transient and resolved without needing medical intervention.
BMO Capital Markets agreed in a Sunday note that these data position ORX750 as a “best-in-class” therapy for narcolepsy, with a “strong/differentiated effect even at 8hrs post-dosing.” BMO analysts also put Centessa’s cash runway at about $480 million, which they said will drive a Phase II readout for ORX750 sometime in 2025 and take the company into 2027.
BMO added that this best-in-class potential “renders [Centessa] an M&A target,” particularly for pharma companies already involved in sleep disorders in the $15 billion market.
Beyond these Phase I data, Centessa is also building toward a Phase II readout for ORX750 this year, which BMO also expects to “demonstrate best-in-class” performance—or the “safest profile, with the lowest dose amount,” —across multiple types of narcolepsy. In turn, ORX750 could drive a 30% to 50% upside for Centessa this year, as per the Sunday note.
Narcolepsy is a neurological disorder involving dysfunctional sleep-wake cycles and most commonly manifests as daytime sleepiness. There are two main types of narcolepsy based on the presence of cataplexy, or sudden muscle weakness: type 1, which involves excessive sleepiness with cataplexy, and type 2, which does not involve cataplexy.
ORX750 works by binding to and activating the orexin receptor 2, a protein in the brain involved in maintaining wakefulness. According to Centessa’s website, its orexin receptor agonists are designed to target the underlying cause of narcolepsy, easing excessive sleepiness, while also demonstrating potential for other symptoms such as inattention, cognitive deficit and fatigue.
