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These events were generally mild to moderate in severity and included: Nausea often accompanying changes in bowel habits, particularly after dose escalation Diarrhoea loose or watery stools, sometimes with urgency Vomiting less common but reported, especially at higher doses Constipation occurring in some individuals, reflecting the variable effect on gut motility Abdominal discomfort or bloating a sensation of fullness or cramping Flatulence increased wind, which can accompany altered digestion Gastrointestinal adverse events were the most common reason for discontinuation in the Phase 2 trial, occurring in approximately 510% of participants depending on dose group

Acknowledgments The author is grateful to the communities of structural biology, biophysics, medicinal and computational chemistry and algorithm design, for the continued accumulation of knowledge and data for drug discovery & design, and for the continued development of tools (hardware, software and algorithm) for drug discovery & design.

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