Centessa IPO Presentation Deck

ZF874: Increased Plasma Levels of Z-A1AT, Reduced Liver Accumulation and Pathology in PiZ Mice DOSED IN DRINKING WATER FOR 28 DAYS Z-A1AT levels were increasing at end of treatment day 28 8mg/ml %change from baseline 200- % change from baseline 12 16 20 Day Fold change relative to vehicle on day 28 7.6x 600- 500- 400- 300- 200- 100- 0- Vehicle 4.9x 2 mg/ml 6.4x 4 mg/ml 2 mg Vehicle 8 mg/ml DOSED IN CHOW FOR 12 WEEKS Z-A1AT Polymer Accumulation in Piz mice PAS-D (% Area Staining) 25 19 13 6 D Marker of Liver Damage ALT Activity (U/L) 30 15 8 D Vehicle Observed 7.6x increase falls in range of predicted 7 to 10x required for full correction ZF874 Vehicle ZFR74 Vehicle 2F874 WT Mice PIZ Mice Z-A1AT Polymer Accumulation (PAS-D Staining of Liver Sections) vehicle ZF874 Marker of Liver Fibrosis in Piz mice Sirius Red (% Fibrosis) 2 20 Marker of Liver Inflammation Normalised TIMP-1 Levels 40 30 10 Vehicle D ZFactor ZF874 ZF874 reduced formation of new Z-A1AT polymers and associated with natural liver clearance mechanisms to remove existing polymers Vehicle 2F874 Vehicle 2F874 WT Mice PIZ Mice CENTESSA 23

View entire presentation