Centessa Pharmaceuticals (CNTA) Jefferies Global Healthcare Conference summary

Orexin program and ORX750 development

• ORX750 is a potent, highly selective orexin 2 agonist designed for narcolepsy and broader sleep-wake disorders, leveraging proprietary crystal structure-based drug design.

• Preclinical data show best-in-class potential, with high potency, selectivity, CNS penetration, and unbiased agonism, supporting efficacy in both NT1 and non-orexin loss indications.

• Safety profile is robust, with extensive preclinical screening showing minimal off-target effects and no hepatotoxicity; adverse events like polyuria and mild blood pressure increases are considered on-target and manageable.

• Accelerated phase I design uses real-time sleep studies in healthy volunteers, enabling rapid dose optimization and early proof-of-concept, with data expected in the second half of 2024.

• The program is positioned as a franchise, with additional molecules in development and flexibility to target multiple sleep-related indications and combination therapies.

Market opportunity and competitive landscape

• NT1 and NT2 have a combined US prevalence of about 150,000, but only 25% are diagnosed and treated, indicating significant unmet need.

• Current treatments often require polypharmacy, and orexin agonists show transformative effect sizes, potentially offering a functional cure for narcolepsy.

• Market opportunity is substantial, with branded narcolepsy drugs generating over $2 billion in revenue; a single molecule effective across rare hypersomnias could be highly impactful.

• The orexin agonist class is validated by recent clinical data, and expansion beyond narcolepsy into broader sleep disorders and related conditions is anticipated.

SerpinPC for hemophilia

• SerpinPC is a first-in-class therapy targeting both hemophilia A and B, with a novel mechanism that reduces bleeding without increasing thrombotic risk.

• Three years of data show 96% bleeding reduction and no evidence of pathological clotting; initial focus is on hemophilia B, where unmet need is highest.

• Ongoing PresEnt-2 and PresEnt-3 studies are progressing, with interim data on dose selection expected this year and primary endpoint data to follow.

• Market for hemophilia B is estimated at $2.5 billion, with SerpinPC aiming to replicate the transformative impact seen with Hemlibra in hemophilia A.