Centessa Pharmaceuticals (CNTA) 7th Annual Evercore ISI HealthCONx Conference summary

Key data and clinical insights

• Recent data position the orexin agonist as best-in-class for wakefulness, with strong effect size and safety profile, showing minimal on-target adverse events similar to placebo across tested doses from 1mg to 5mg.

• Benefits extend beyond narcolepsy to excessive daytime sleepiness, cognition, memory, attention, and executive function, suggesting broad potential indications.

• ORX750, now in phase II for NT1, NT2, and IH, demonstrates exceptional pharmacokinetics, linear dose-exposure-response, and a wide therapeutic index.

• Next-gen molecules ORX142 and ORX489 show even greater potency and selectivity, enabling lower dosing and reduced risk of drug-drug interactions, supporting expansion into neurodegenerative and neuropsychiatric disorders.

• Selectivity for orexin receptor 2 exceeds 10,000x over receptor 1, minimizing off-target effects and supporting a favorable safety profile.

Clinical development strategy and timelines

• Phase II for ORX750 is ongoing in the U.S., with adaptive dosing and real-time data review to optimize dose selection for phase III.

• Phase I and II data, including multi-dose cohorts, will be presented at a conference in 2025; phase II efficacy data for NT1, NT2, and IH are also expected in 2025.

• ORX142 is expected to enter the clinic in 2025, targeting broader indications beyond rare hypersomnias.

• The development approach emphasizes rapid progression, small proof-of-concept studies, and flexible trial design to inform pivotal phase III studies.

• Data visibility is maintained on a blinded basis, with high confidence in safety and efficacy to date.

Commercial and strategic considerations

• The rare hypersomnia market is estimated at $5–$6 billion, and the company is positioned to pursue this space independently.

• Broader indications in neurodegenerative and neuropsychiatric disorders may require partnerships due to the scale of opportunity.

• Flexibility is retained to either go solo or seek partners, depending on future data and market opportunities.

• The hemophilia program was discontinued for strategic reasons, not due to safety concerns, and may be out-licensed for further development.