Centessa Pharmaceuticals (CNTA) investor relations material

Key program updates and scientific insights

• Significant progress in the orexin agonist program, with ORX-750 and ORX-142 advancing in clinical development.

• Orexin agonists are positioned as transformative for narcolepsy and other hypersomnias, targeting the underlying cause rather than symptoms.

• ORX-750 features a flexible, once-daily dosing profile, with proprietary design based on crystal structure insights.

• Phase 2a CRYSTAL-1 study uses adaptive, real-time dose optimization across NT1, NT2, and IH, aiming for best-in-class efficacy and tolerability.

• Data from ORX-142, a more potent molecule, is expected this year, with potential for broader neurodegenerative and neuropsychiatric indications.

Clinical data and competitive landscape

• Phase 1 data for ORX-750 showed strong maintenance of wakefulness and favorable safety, with minimal difference from placebo.

• Higher doses are needed for NT2 and IH due to intact orexin systems, while NT1 requires lower doses.

• Competitor data at World Sleep Congress reinforced confidence in the program and highlighted commercial focus.

• Aim to launch one molecule across all three indications, simplifying treatment for physicians and patients.

• Enthusiasm among physicians is high, with expectations that orexin agonists could redefine standards of care.

Market opportunity and financial position

• Rare hypersomnias represent a market opportunity exceeding $15 billion, with NT1 alone estimated at $6–7 billion.

• Cash position of $400 million as of June 30, providing runway into mid-2027.

• Intellectual property strategy and medicinal chemistry expertise provide a competitive moat in the orexin agonist space.

• AI is leveraged in clinical operations, but human relationships remain central to execution.

• Regulatory and tariff risks are considered manageable, with contingencies in place.