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

Pipeline overview and strategic focus

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

• ORX750, a potent orexin-2 receptor agonist, is positioned as a potential best-in-class therapy for narcolepsy and related disorders, aiming to address the underlying disease cause rather than just symptoms.

• ORX142, the next orexin molecule, is advancing toward clinical development for indications with normal orexin levels, with primate data to be presented soon.

• The SerpinPC program targets hemophilia with a novel mechanism, offering subcutaneous dosing and strong efficacy in reducing bleeding rates.

• LB101, a PD-L1/CD47 bispecific, is in phase I, focusing on validating its tumor-selective activation and safety profile.

ORX750 and orexin franchise development

• ORX750 demonstrates high potency (110 picomolar) and selectivity, with preclinical studies showing strong brain penetration and once-daily dosing potential.

• The phase I study uses an innovative design combining single ascending dose and sleep studies to rapidly identify optimal dosing for narcolepsy type 1, type 2, and idiopathic hypersomnia.

• Safety screening has been extensive, with clean GLP toxicology results in both rodents and non-rodents, supporting confidence as clinical trials progress.

• Differentiation is based on once-daily dosing, low predicted human doses, achieving normative wakefulness, and a favorable safety/tolerability profile.

• Proof-of-concept data in sleep-deprived healthy volunteers is expected by year-end, aiming to inform future clinical development.

SerpinPC in hemophilia

• Phase II data show SerpinPC reduces annualized bleeding rates by over 90%, with no sustained D-dimer elevation or thrombus formation observed to date.

• The drug offers a convenience advantage with subcutaneous administration compared to standard IV factor replacement.

• 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 in part two of PRESent-2 is reduction in bleeding rates in on-demand subjects after six months of SerpinPC treatment.

• Differentiation centers on unique mechanism, safety profile, and absence of thrombosis, addressing key challenges in the hemophilia treatment landscape.