BenevolentAI Investor Day Presentation Deck

BEN-8744 - Phosphodiesterase 10 (PDE10) - a novel target for UC Transcriptomics data support the rationale for PDE10 as a novel target for UC ● PDE10 regulates signal transduction by hydrolysing cGMP PDE10 is significantly upregulated in UC-derived colon and colonic mucosa samples, whilst guanylyl cyclase, which makes CGMP, is down-regulated Reduced levels of guanylyl cyclase correlate with increased TNF-a in UC colonic mucosa (¹) CGMP is downregulated in UC and its expression inversely correlates to disease severity ● PDE10 is well-studied in CNS disorders but not in inflammation with zero linkage to UC PDE10 demonstrates restricted expression in peripheral tissue Reduces the safety liability of targeted inhibition nitric oxide synthase arginine soluble guanylyl cyclase NOS NO readily diffuses across plasma membranes NO activates GC GTP CGMP activates protein kinases and other proteins breaks down phosphodiesterase e.g. PDE10 PDE10 degrades cGMP Source: (1) Brenna et al. Scand J Gastroenterol 2015 Image (left): Rashed, Second Messenger System 2018 GUCY2C • LogFC PDE 10A LogFC Differential RNA expression of PDE10A and GUCY2C: normal vs UC colonic mucosa colon log FPKM Adipose ww pose Tissue Adrenal Gland Bladder Blood Blood Vessel Brain Breast Cervix Uteri Colon Esophagus Fallopian Tube Heart RNAseq Lun Liver Tissue Nerve M Ovary Pancreas Pituitary Prostate Salivary Gland Skin Intest Small Spleen Stomach Testis Low basal PDE10 expression, highest levels in brain. Low basal soluble guanylate cyclase (GUCY2C) levels except in colon and sm intestine Gene 8 MI PDEGA PDE10A GUCY2C Benevolent 57

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