Summary of Centessa Pharmaceuticals FY Conference Call Company Overview - Centessa Pharmaceuticals is a clinical-stage biotech company focused on orexin biology and orexin agonism, particularly in the treatment of sleep disorders such as narcolepsy and idiopathic hypersomnia [2][3] Key Developments - The company recently updated its Phase 2 study results involving approximately 50-55 patients across Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) [2][3] - Centessa is the first company to present a robust dataset demonstrating statistically significant efficacy across all three indications [2][3] Pipeline and Future Studies - The lead asset, ORX750, is currently in Phase 2, with additional molecules ORX142 and ORX489 entering Phase 1 studies in Q1 2026 [3][4] - The company aims to expand beyond rare hypersomnias into neurodegenerative and psychiatric conditions [4] Efficacy Data - In NT1, a second dose of 1.5 mg showed a greater than 20-minute change from baseline in the Maintenance of Wakefulness Test (MWT), with half of the patients showing over 30 minutes improvement [6][7] - For NT2, a 4 mg dose resulted in a greater than 10-minute change from baseline, with the Epworth Sleepiness Scale (ESS) improving from 15-16 to 8 [7][8] - In IH, the initial 2 mg dose demonstrated clinically significant improvements in MWT and other efficacy measures [8] Safety and Tolerability - The drug has shown a favorable safety profile, with no significant adverse events reported, and only one dropout due to a pre-existing condition [31][32] Registration Program - The registration program is set to commence in Q1 2026, with flexibility to initiate across all three indications or staggered based on data from the next 50 patients [27][28] Competitive Landscape - The company believes it has a best-in-class profile based on the totality of evidence, including MWT, ESS, and tolerability metrics [34] - The orexin agonist class is viewed as having significant potential, akin to GLP-1 in the field of neurosciences [37] Intellectual Property - Centessa has developed a strong IP portfolio, with protections extending past 2040, based on unique structural biology technology [40] Conclusion - Centessa Pharmaceuticals is positioned to make significant advancements in the treatment of sleep disorders and potentially other neuropsychiatric conditions, with promising data from its lead asset and a robust pipeline [42]

Financial Performance - FY2025 Q1 revenue was JPY 1,1067 billion, a decrease of 84% compared to FY2024 Q1[16] - FY2025 Q1 core operating profit was JPY 3218 billion, a decrease of 158% compared to FY2024 Q1[16] - FY2025 Q1 reported operating profit increased by 110% to JPY 1846 billion, primarily due to lower impairment and restructuring expenses[16, 28] - Adjusted free cash flow for FY2025 Q1 was JPY 1901 billion, a significant increase of 7036% compared to FY2024 Q1[16] - Takeda maintains its FY2025 forecast with revenue of JPY 4,5300 billion, a decrease of 11%[34] Portfolio Performance - Growth & Launch Products increased by 50% at CER in Q1[18] - Growth & Launch Products accounted for JPY 5581 billion (USD 39 billion), representing 50% of total revenue[19] - VYVANSE revenue is expected to decline by JPY 1096 billion (-30% at CER) in FY2025[34] Pipeline and Milestones - Oveporexton (TAK-861) Phase 3 met all primary and secondary endpoints, showing transformative potential in NT1[40] - Zasocitinib is in Phase 3 for Psoriasis with a head-to-head start vs deucravacitinib[46, 49] - Rusfertide is targeting US filing for Polycythemia Vera in H1 FY25[49]