Centessa's oral OX2R agonist ORX750 preclinically reduces cataplexy and promotes wakefulness in narcolepsy mouse model

Centessa Pharmaceuticals plc

ORX750 is a potent full agonist at human OX2R (EC50=0.11 nM) with >9,800-fold selectivity over OX1R.
In orexin/ataxin-3 narcolepsy mice, ORX750 increased wakefulness and consolidated wakefulness dose-dependently.
At 0.3 mg/kg, latency to sleep was 2.3 h (vs 0.69 h vehicle) and latency to cataplexy was 2.7 h (vs 1.3 h vehicle).
ORX750 also increased EEG gamma power during wakefulness and reduced cataplexy occurrences in active-phase EEG/EMG assays.
Company will present abstract at World Sleep Congress 2023 on October 25, 2023.

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