Centessa Pharmaceuticals (CNTA) Guggenheim Securities Inaugural Healthcare Innovation Conference summary

Key clinical data and study results

• ORX750 demonstrated a favorable safety profile at higher doses in both single and multiple ascending dose studies, with linear dose-response and increasing efficacy versus placebo.

• Multiple ascending dose studies showed higher drug exposures and maintained safety, aligning with proof-of-concept data.

• Efficacy was confirmed by increased mean wakefulness times and larger deltas versus placebo at higher doses.

• The molecule’s design, with a lower Cmax to trough ratio, aimed to minimize on-target adverse events, validated in clinical data.

• No significant increase in adverse events was observed compared to placebo, supporting the molecule’s differentiated safety profile.

Pipeline strategy and market opportunities

• The Orexin pathway is validated for excessive daytime sleepiness, with broad potential across rare hypersomnias and other CNS disorders.

• Multiple molecules are being developed to address distinct indication buckets, with ORX750 targeting rare hypersomnias and new candidates like ORX489 showing high potency.

• The strategy includes developing molecules for both rare and high-prevalence disorders, considering polypharmacy and minimizing drug-drug interaction risks.

• Research efforts are focused on continually generating high-quality, potent molecules to expand into broader CNS indications.

• Commercial strategy involves positioning molecules for both rare disease pricing and broader, high-volume markets.

Phase II and future clinical development

• Phase II study design is innovative, allowing flexible dose selection and rapid recruitment by minimizing placebo exposure and including basket cohorts for NT1, NT2, and IH.

• Efficacy, safety, and PK data are integrated in real time to guide dose escalation and optimize registrational study planning.

• Randomized withdrawal is incorporated to assess effects post-treatment, with potential for use in pivotal studies.

• Data for NT1, NT2, and IH are expected in 2025, with a focus on execution and rapid data generation.

• Total patient exposure across all phases will inform the safety package for regulatory approval.