Centessa Pharmaceuticals (NasdaqGS:CNTA) 2025 Conference November 18, 2025 09:00 AM ET Company ParticipantsMario Alberto Accardi - President of Orexin ClassConference Call ParticipantsClara Dong - Biotech AnalystClara DongThanks for joining Jefferies Global Healthcare Conference in London. My name is Clara Dong, one of the biotech analysts at Jefferies here. Sitting next to me, we have Dr. Mario Alberto Accardi, the President of Orexin Class from Centessa Pharmaceuticals. Welcome.Mario Alberto AccardiThank ...

Summary of Centessa Pharmaceuticals FY Conference Call Company Overview - **Company**: Centessa Pharmaceuticals (NasdaqGS:CNTA) - **Event**: FY Conference on November 12, 2025 - **Presenters**: Saurabh Saha (CEO), Mario Accardi (President of the Orexin Program) Key Points Industry and Product Focus - Centessa Pharmaceuticals is not limited to narcolepsy but is exploring broader applications of its drug ORX-750, which targets orexin signaling in various neurological conditions [5][6] - The company has reported positive clinical data for ORX-750 across three indications: Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) [5][6] Clinical Data and Efficacy - ORX-750 has shown clinically meaningful effectiveness in NT1 and NT2, with significant changes in the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) [11][12] - In NT2, a greater than 10-point change from baseline in MWT and a drop in ESS from 16 to 8 were reported, indicating strong efficacy [11][12] - In NT1, a greater than 20-point change from baseline in MWT was observed, with half of the patients at the 1.5 mg dose showing over 30 on mean MWT [12] Drug Development Strategy - Centessa employs a real-time drug development approach, allowing for dose adjustments based on ongoing data analysis [7][8] - The company emphasizes the importance of dose-responsive data and has achieved linear exposure with dose [10] Tolerability and Safety - ORX-750 is reported to be well-tolerated, with mild adverse events (AEs) such as polyuria and insomnia, which are not dose-limiting [15][16] - The drug has shown a favorable pharmacokinetic (PK) profile, allowing for higher dose escalation without significant safety concerns [15][16] Regulatory and Market Position - Centessa plans to initiate its registration program in early 2026, with ongoing discussions with the FDA [49] - The company believes that orexin agonists will serve as monotherapy across NT1, NT2, and IH, addressing a significant unmet clinical need [43][44] Competitive Landscape - Centessa positions ORX-750 as potentially best-in-class based on its clinical data compared to competitors [11][12] - The company aims to differentiate itself by offering a drug with a robust duration of action, reducing the need for polypharmacy in patients [44][45] Future Directions - The company is exploring split dosing to provide flexibility for patients, allowing for better symptom control throughout the day [21][23] - Ongoing studies will refine the understanding of normative wakefulness thresholds and the drug's efficacy across different patient populations [27][28] Market Opportunity - The total addressable market for narcolepsy treatments is larger than current revenue figures suggest, as many patients are on generic medications that do not adequately control symptoms [48] Additional Insights - The company is focused on ensuring rigorous patient selection criteria to avoid confounding data in clinical trials [36][37] - Centessa is committed to addressing the challenges of disturbed nighttime sleep associated with narcolepsy, which is a significant concern for patients [43][44]

Summary of Centessa Pharmaceuticals (CNTA) Conference Call - February 06, 2025 Company Overview - **Company**: Centessa Pharmaceuticals (CNTA) - **Key Participants**: Debjit Chattopadhyay (Managing Director), Mario Accardi (President of the Orexin Program) Core Industry and Company Insights - **Industry**: Pharmaceuticals, specifically focusing on treatments for narcolepsy and excessive daytime sleepiness - **Key Product**: ORX750, an orexin agonist, which has shown promising results in clinical trials Key Points and Arguments 1. **Transformative Year**: 2024 was described as a transformative year for Centessa, with a significant focus on the Orexin program and the development of ORX750 [2][3] 2. **Clinical Trials**: ORX750 has successfully completed a Phase 1 study, demonstrating a best-in-class profile with a mean wakefulness period (MWP) of 38 minutes, significantly outperforming the placebo [3][4] 3. **Phase 2 Studies**: Initiated Phase 2 studies for narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH) in 2024, with data expected in 2025 [4][41] 4. **Safety Profile**: The safety and tolerability profile of ORX750 is reported to be significantly differentiated from other similar drugs, with no relevant pharmacology across other GPCRs [6][7][9] 5. **Dosing Strategy**: The design of ORX750 allows for once-daily dosing, which is expected to maintain wakefulness throughout the day while allowing patients to return to sleep at night [12][13] 6. **Study Design**: The Phase 2 study design is unique, allowing for dose selection based on real-time data from unblinded cohorts, which is different from conventional studies [14][15] 7. **Market Potential**: The potential market for NT2 and IH is estimated to be over $7.5 billion, with additional opportunities in other conditions associated with excessive daytime sleepiness, such as Parkinson's disease and major depressive disorder [32][33] 8. **Future Plans**: The company aims to be first in class for NT2 and IH, with plans to progress each indication independently based on enrollment rates [41][42] Additional Important Insights 1. **Leadership Changes**: The hiring of Steve Caines as Chief Medical Officer is expected to enhance the company's capabilities in the CNS space [5] 2. **Regulatory Strategy**: The company plans to have data ready for an end-of-Phase 2 meeting, which will facilitate the transition to registration studies [41] 3. **Flexibility in Development**: Centessa retains flexibility in its clinical development strategy, allowing for adjustments based on cohort performance and enrollment rates [26][27] 4. **Potential for Partnerships**: While the company has not ruled out partnerships for larger indications, it is confident in its ability to build a successful business model independently [39] This summary encapsulates the key discussions and insights from the conference call, highlighting Centessa Pharmaceuticals' strategic direction, clinical advancements, and market opportunities in the pharmaceutical industry.