m m 0 1 0 2 0 3 0 4 0 v e h i c l e b i d r x c 0 0 5 [ 5 ... · l o g [ r x c 0 0 5 ] ( m ) % i n...

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Log [RXC005] (M) % inhibition -14 -12 -10 -8 -6 -4 -20 0 20 40 60 80 100 120 BTK WT BTK C481S -11 -10 -9 -8 -7 -6 -5 -4 0 20 40 60 80 100 120 Log [RXC005] (M) BTK WT BTK C481S % inhibition -12 -10 -8 -6 -4 0 20 40 60 80 100 120 log[RXC005] (M) % of activated B-cells (IgM-stimulated CD19+ CD69+ cells) -12 -10 -8 -6 -4 -20 0 20 40 60 80 100 120 log[RXC005] (M) % of activated B-cells (IgD-stimulated CD19+ CD69+ cells) pBTK BTK B-Actin γ γ α Cell line OCI-Ly10 (pIC 50 ) 8.2± 9.3±0.2 8.3±0.1 8.4±0.2 TMD8 (pIC 50 ) 8.3± 9.1±0.2 8.3 (N=2) 8.2 (N=2) IgM stimulation pBtk gapdh Btk 00251868 CLL Vehicle 200 nM RXC005 500 nM Ibrutinib Vehicle DC9 (+ control) 500 nM RXC005 100 nM RXC005 0 10 20 30 40 1.0 1.5 2.0 Days post last treatment RTV (Relative Tumour Volume) **** *** *** **** p<0.0001 *** p<0.001 0 20 40 60 Days Tumour volume (mm 3 ) Vehicle BID RXC005 [10mg/kg] BID RXC005 [50mg/kg] BID Ibrutinib [10mg/kg] QD 200 300 400 500 150 100 Treatment Regrowth 0 10 20 30 Treatment time (Days) Tumour volume (mm 3 ) Vehicle BID RXC005 10 mg/kg BID RXC005 50 mg/kg BID Ibrutinib 10mg/kg QD 200 300 400 500 150 100 **** **** p<0.0001 *** *** p<0.001 0 7 14 21 Treatment time (days) Tumour volume (mm 3 ) Vehicle RXC005 30mg/kg BID 100 200 400 RXC005 10mg/kg BID 800 1000 **** p<0.0001 **** ****

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Page 1: M m 0 1 0 2 0 3 0 4 0 V e h i c l e B I D R X C 0 0 5 [ 5 ... · L o g [ R X C 0 0 5 ] ( M ) % i n h i b i t i o n - 1 4 - 1 2 - 1 0 - 8 - 6 - 4 - 2 0 0 2 0 4 0 6 0 8 0 1 0 0 1 2

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