Centessa Pharmaceuticals (CNTA) Jefferies London Healthcare Conference 2024 summary

Program overview and recent data

• Focus on developing orexin agonists for sleep-wake disorders, with ORX-750 in phase II trials and recent positive healthy volunteer data showing strong efficacy and safety at higher doses.

• Multi-dose studies at 2mg and 3mg showed adverse events similar to placebo, and higher doses (3.5mg, 5mg) maintained a favorable safety profile.

• Phase II study design aims for rapid, informative dose selection using a basket approach across NT1, NT2, and IH, with adaptive cohort unblinding to optimize dosing.

• Unblinded phase II data for NT1, NT2, and IH expected in 2025; additional phase I data for 5mg dose to be presented at a conference next year.

• ORX-750, ORX-142, and ORX-489 are distinct chemical entities, with 142 and 489 targeting high-prevalence disorders and aiming for sub-milligram dosing to minimize drug-drug interactions.

Market opportunity and competitive positioning

• Rare hypersomnias (NT1, NT2, IH) represent a market opportunity north of $5 billion, while high-prevalence disorders like major depressive disorder and Parkinson's could exceed $10 billion.

• Orexin agonists may address not only sleep-wake symptoms but also mood, cognition, and fatigue, expanding their potential indications.

• Current standard of care does not address the root cause; orexin agonists could offer functional cures with significant improvements in patient quality of life.

• Multiple assets enable tailored commercial strategies for different indications and patient populations.

• Company is well-funded with over $500 million in cash, supporting operations and clinical milestones into mid-2027.

Scientific and clinical differentiation

• ORX-750 designed for high selectivity (9,800-fold for orexin 2 over orexin 1) to minimize off-target effects and maximize efficacy.

• Dose linearity observed in efficacy without increased on-target adverse events, attributed to molecule design and narrow Cmax-to-trough ratio.

• Selective orexin 2 activation shown to relieve all symptoms in NT1, improve sleep architecture, and avoid reward-seeking behaviors linked to orexin 1.

• Phase II studies use comprehensive efficacy measures, including sustained attention and cognition, to optimize dose selection.

• Enrollment strategies minimize placebo exposure, encouraging patient participation and faster study completion.