Summary of Alkermes (ALKS) FY Conference Call - June 09, 2025 Company Overview - Alkermes has evolved from a narrow focus on neuroscience to a broader drug delivery company, now generating a billion-dollar top line revenue driven by proprietary products [3][4][5] - The company aims to create new molecules that address unmet medical needs, particularly in the neuroscience space related to the sleep-wake cycle and circadian rhythm [4][5] Core Business and Pipeline - The current focus is on the REXN portfolio, particularly the orexin opportunity, which is seen as a new frontier in the field [6][7] - The company has a strong technical capability in chemistry, essential for developing complex molecules in the orexin space [5][6] - The commercial business is profitable and funds the pipeline, with expectations for growth and expansion over time [5][6] Clinical Trials and Data - Phase 1b study results showed a clear dose-dependent increase in maintenance of wakefulness in narcolepsy type 1 (NT1) patients, with no discontinuations due to adverse events (AEs) [11][12][32] - Phase 2 studies (Vibrance 1 and 2) are expected to provide further insights into tolerability and efficacy across different doses and patient populations [14][15][18] - The primary endpoints for the Vibrance studies include maintenance of wakefulness test (MWT), cataplexy rates, and sleepiness scales [26][48] Market Opportunity - The prevalence of NT1, NT2, and idiopathic hypersomnia (IH) patients is significant, yet only a fraction are currently treated, indicating a large market opportunity for orexin agonists [48][49] - The company anticipates deep penetration in the NT1 market due to its disease-modifying properties, while NT2 and IH may see varying levels of uptake based on patient needs and drug costs [49][50] - The potential for combination therapy with existing treatments is still under evaluation, with the expectation that orexin agonists could become frontline therapies for NT1 [56][58] Commercial Strategy - Alkermes plans to commercialize the orexin agonist globally, with a focus on maintaining high pricing reflective of its disease-modifying capabilities [66][67] - The company expects a high percentage of commercial payers (around 80%) for NT1, NT2, and IH patients, contrasting with its existing portfolio which is largely Medicaid and Medicare [70][71] - The commercial portfolio is performing well, with growth expected from existing products like Livaldi, ARISTADA, and VIVITROL [72][74] Conclusion - Alkermes is positioned to capitalize on the growing demand for innovative treatments in the sleep disorder market, with a strong pipeline and commercial strategy aimed at addressing significant unmet needs in NT1, NT2, and IH patients [48][49][72]

Summary of Centessa Pharmaceuticals (CNTA) Conference Call Company Overview - **Company**: Centessa Pharmaceuticals (CNTA) - **Focus**: Orexin program, specifically ORX750, an orexin agonist for treating narcolepsy and idiopathic hypersomnia Key Insights on Orexin Space - **Exciting Year Ahead**: Centessa anticipates a data-rich year with multiple catalyst events, including Phase II data disclosures for narcolepsy type one, type two, and idiopathic hypersomnia with ORX750, which is considered the most potent and selective orexin agonist in clinical development [2][4] - **First in Class Opportunity**: The company aims for a first-in-class opportunity in narcolepsy type two and idiopathic hypersomnia, with a best-in-class profile characterized by rapid onset of action, potential for QT dosing, linear pharmacokinetics (PK), and flexible dosing [2][4] Phase II Study Design - **Innovative Design**: The Phase II study allows for dose selection during the study based on real-time data, enabling optimal dosing and flexibility for patients [2][3] - **Efficacy Data**: Preliminary data from sleep-deprived healthy volunteers showed significant efficacy, with patients on ORX750 maintaining wakefulness significantly longer than those on placebo [7][8] Safety and Tolerability - **High Tolerability**: The drug class is reported to be extremely well tolerated, with minimal on-target adverse events (AEs) such as insomnia and polyuria [15][16] - **Liver Toxicity Concerns**: Centessa emphasizes that liver toxicity is molecule-specific and not an on-target effect, focusing on developing molecules with a favorable metabolic profile to mitigate risks [20] Market Opportunity - **Large Patient Population**: The company has revised epidemiological numbers, identifying approximately 50,000 diagnosed and treated narcolepsy type one patients, 100,000 in type two, and 120,000 in idiopathic hypersomnia, indicating a substantial market opportunity [24][25] - **Potential for Multiple Agonists**: There is potential for more than one orexin agonist in the market, given the large patient population and unmet clinical needs [25] Future Directions - **Expansion into Other Indications**: Centessa plans to explore orexin agonists in neurodegenerative and psychiatric disorders, such as Parkinson's disease and major depressive disorder, where excessive daytime sleepiness is prevalent [36][37] - **Partnership Opportunities**: While currently fully financed to execute clinical development plans, the company remains open to partnerships for indication expansion in the future [38] Conclusion - **Transformational Potential**: The orexin agonist class, particularly ORX750, is positioned to significantly impact the treatment landscape for narcolepsy and other disorders characterized by excessive daytime sleepiness, with a strong focus on patient needs and flexible dosing strategies [36][37]