Centessa Pharmaceuticals (CNTA) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Program updates and clinical pipeline

• Three clinical programs are active, with a strong focus on orexin agonists for sleep-wake disorders and a robust cash position of $300 million.

• ORX750, an orexin-2 receptor agonist, aims to address the underlying cause of narcolepsy and related disorders, with proof-of-concept data expected by year-end.

• ORX142, a second orexin agonist, is advancing toward clinical studies targeting excessive daytime sleepiness in broader indications, with primate data to be presented soon.

• SerpinPC, a novel hemophilia therapy, has shown over 90% reduction in bleeding rates and is administered subcutaneously, offering a convenience advantage.

• LB101, a PD-L1/CD47 bispecific, is in phase I dose escalation to validate its tumor-targeted mechanism and safety profile.

Differentiation and competitive positioning

• ORX750 is highly potent (110 picomolar), with a design focused on once-daily dosing, low predicted human doses, and minimized Cmax to trough ratio for safety.

• Preclinical safety panels and GLP tox studies for ORX750 have been clean, supporting confidence as it enters clinical trials.

• The orexin franchise aims for broad application, including narcolepsy types 1 and 2, idiopathic hypersomnia, and conditions with normal orexin levels.

• SerpinPC’s unique mechanism avoids sustained D-dimer elevation and thrombosis, differentiating it from competitors and supporting a favorable therapeutic index.

• LB101’s design ensures systemic safety and tumor-specific activation, with ongoing monitoring for anemia and thrombocytopenia as key safety endpoints.

Clinical development and future plans

• ORX750’s phase I study uses an innovative design combining single ascending dose and sleep studies to rapidly identify optimal dosing for multiple indications.

• Plans include developing ORX750 for NT1, NT2, and IH, with ORX142 targeting broader sleepiness-related disorders such as Parkinson’s, depression, and sleep apnea.

• SerpinPC’s PRESent-2 and PRESent-3 studies are progressing, with interim dose selection data expected later this year and full data by early next year.

• The primary endpoint for SerpinPC is reduction in annualized bleeding rates in hemophilia B patients, with part two of the study already enrolling.

• LB101’s phase I will assess both systemic safety and tumor efficacy, with results to inform further development.