Centessa Pharmaceuticals (CNTA) Goldman Sachs 45th Annual Global Healthcare Conference summary

R&D strategy and portfolio focus

• Three clinical programs are active, with a strong emphasis on data-driven R&D and assets with transformative potential.

• Asset selection is based on potential impact, not limited by therapeutic area or modality.

• The orexin agonist franchise is being built with multiple molecules, aiming for broad indications beyond narcolepsy.

• Structure-based design and proprietary chemistry underpin the orexin program's innovation.

• Go/no-go decisions are made expeditiously, with a focus on optimal effect size and safety for chronic use.

Orexin agonist program (ORX-750)

• ORX-750, a best-in-class orexin 2 receptor agonist, has entered phase I trials, generating significant excitement.

• The drug targets excessive daytime sleepiness (EDS) in narcolepsy and potentially other disorders like Parkinson’s, MDD, and sleep apnea.

• Phase I uses a unique crossover design in healthy volunteers, measuring wakefulness and safety at early stages.

• The molecule was selected for rapid onset, potency, brain penetration, and favorable drug-drug interaction profile.

• Safety focus includes differentiated metabolic profile and minimized risk of DILI and on-target adverse events.

Clinical trial design and future plans

• The phase I study design allows for iterative dose escalation and early proof-of-concept data, expediting development.

• Data from healthy volunteers is expected in the second half of the year, with plans to move quickly into broader indications.

• Flexibility in indication selection post-phase I, with potential to pursue both rare and common EDS-related disorders.

• Future studies will prioritize speed, safety, and innovative trial designs over conventional approaches.

• The franchise approach allows for multiple products with varied PK profiles for different patient needs.