Centessa Pharmaceuticals (CNTA) investor relations material

Vision and strategy for orexin agonists

• Focus on developing orexin agonists for rare hypersomnias, including narcolepsy type 1, type 2, and idiopathic hypersomnia, with plans to expand into broader neuroscience indications.

• Transitioning to a pre-commercial stage with a robust pipeline of potent and selective orexin agonists enabled by a proprietary structural biology platform.

• Emphasis on achieving best-in-class status not only against current competitors but also future entrants in the orexin agonist space.

• Strategy includes both once-daily and split dosing to maximize patient flexibility and efficacy.

• Commercial planning and hiring are underway as the company prepares for registration studies and broader market entry.

Clinical development and data-driven decisions

• Registrational studies for at least one, potentially all three, rare hypersomnia indications are planned to start this quarter, pending final dose selection.

• Dose selection is guided by ongoing Phase II data, with flexibility to add cohorts if further efficacy can be achieved.

• Maximum tolerated dose is being explored, with insomnia as a potential limiting factor, to provide optimal dosing flexibility for patients.

• No regulatory barriers exist for study initiation; positive FDA feedback and alignment on clinical strategy have been received.

• Randomized withdrawal study designs, favored by European regulators, are under consideration for future protocols.

Efficacy, endpoints, and competitive positioning

• ORX750 has demonstrated best-in-class efficacy in NT1 and NT2, with significant improvements in wakefulness and cataplexy reduction.

• In NT2, achieving a greater than 10-minute change from baseline on the MWT and normalizing ESS scores are key efficacy targets.

• For idiopathic hypersomnia, the goal is to achieve clinically meaningful reductions in ESS and improvements in IHSS, addressing a large unmet need.

• The company aims to provide a monotherapy solution for narcolepsy type 1, addressing all major symptoms, with ongoing exploration of sleep quality endpoints.

• Regulatory acceleration measures, such as Breakthrough Therapy Designation, are being actively evaluated.