Benevolent Platform Precision Medicine

Target R: Chemistry progressed to deliver a potent, selective and highly brain penetrant molecule AIChemOpt Prep & Hit ID / Expansion AIChemOpt Lead Optimisation Feb 2020 9m Nov 2020 12m Nov 2021 Candidate Seeking May 2022 6m Hit ID BEN-9677 Hit-to-Lead BEN-11156 Lead Optimisation Lead compound(s) PIC50 (LLE) Pfizer CNS MPO 6.1 (5.2) 5.4 PIC50 (LLE) Kinases IC50 <1 μM Cerep >50% @ 1μM hERG IC50 (µM) 7.9 (6.7) 6/372 1/87 >30 PIC50 (LLE) Selectivity Efflux ratios ADME >9 (>8.0) Excellent Low / none Good Efflux ratio MDR1/BCRP Крии (rat) 1.7/3.7 0.44 Brain-penetrant Radiosensitiser Yes Yes Novel kinase hinge binder Retained key motif for selectivity From BAI virtual screen Patent ID and data extraction Controlled substance checker Oral bioavailability (%) 51 On-/off-target docking models Reaction enumeration Predictive model suite • о Activity, metabolism, efflux Generative chemistry Advanced profiling underway Upcoming milestone: GBM xenograft TE study Potent backup series with low efflux also in development Our lead series represents a potent, selective and highly brain-penetrant ‘Target R' kinase inhibitor Benevolent 56 Al

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