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Long-Term Efficacy and Safety While 68-week data from REDEFINE trials provide substantial evidence, longer-term questions persist: Duration beyond 68 weeks requires further study to establish maintenance of weight loss Cardiovascular outcomes data pending from the ongoing REDEFINE 3 trial (expected completion in future years) Long-term safety profile beyond the studied durations incompletely characterized Weight regain patterns after discontinuation not fully elucidated Mechanistic Understanding Gaps Fundamental aspects of cagrilintide’s mechanism warrant further investigation: Relative contribution of CTR versus AMYR activation to clinical effects remains incompletely defined Tissue-specific receptor expression and activity in humans requires clarification Optimal receptor selectivity profile for various patient populations unknown Interaction effects with other metabolic pathways not fully characterized Clinical Application Questions Practical considerations for therapeutic use require additional research: Patient selection criteria for monotherapy versus combination approaches Comparative effectiveness versus other obesity medications in real-world settings Management strategies for gastrointestinal adverse events Combination potential with medications beyond GLP1 Regulatory & Clinical Development Status FDA and Regulatory Position Cagrilintide remains investigational as of September 2025: Not FDA-approved for any indication as of current date Phase 3 programs completed with results published in New England Journal of Medicine June 2025 Dedicated RENEW phase 3 program for cagrilintide monotherapy announced for initiation Q4 2025 Regulatory submissions anticipated following completion of development programs Combination therapy (CagriSema) also under development for potential future approval WADA Status Information on World Anti-Doping Agency classification not specified in available research literature

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What to Expect Before Starting the KLOW Program Every KLOW program begins with a medical evaluation