Benevolent Platform Precision Medicine

BEN-8744 is a highly potent and selective PDE10 inhibitor Primary Pharmacology¹ Safety Pharmacology' Human PDE10 IC50 (biochem <InM HERG IC50 13uM & cell-based assays) CaV1.2 IC50 >30uM Mouse PDE10 IC50 <InM Nav1.5 Ic50 >30uM IC50 in IBD biopsy <InM inflammatory cytokine Human iPSC-derived No flags release assay (UC & Crohn's) cardiomyocyte toxicity Selectivity vs other PDE ≥1000 fold family members Selectivity vs broad panel of safety targets (Cerep87) ≥1000 fold Highly potent Good selectivity No safety flags Ames (5 strain, +/- S9) IVMN Hepatic toxicity (hepatocyte cytotoxicity; DILI panel, 14 day 3D liver organoid assay) 7 day rat toxicology study Negative Negative Negative No overt toxicity or clinical observations >100x predicted hAUC Al Benevolent 42 1 Company internal drug programme data

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