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and (3) early oxyntomodulin analogs, which were discontinued in part because regulatory endpoints for combination receptor agonism had not yet been established ( 8.1 Regulatory expectations and evidence standards Regulatory agencies increasingly emphasize mechanism-anchored development supported by robust pharmacodynamic biomarkers and clinically meaningful endpoints ( A recurring integrity issue in peptide development has been premature extrapolation from animal models to humans

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Such direct inhibitory action appears surprising for a peptide thought to be primarily involved in sleep promotion

Compounds 27 - 29 (Figure 23) reduced A oligomerization, while compounds 30 and 31 (Figure 23) inhibited A fibrillization

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