EFFECTS OF RN316 (PF-04950615), A HUMANIZED IGG2[delta]A MONOCLONAL ANTIBODY BINDING PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9, ON LIPOPROTEIN PARTICLES IN HYPERCHOLESTEROLEMIC SUBJECTS

Day 36a (Study #1) Day 71a (Study #2 and #3) RN316 Groups (Number of subjectse) Placebo (n=12) 0.25 mg/kg (n=13) 0.5 mg/kg (n=13) 1 mg/kg (n=12) 1.5 mg/kg (n=14) Placebof (n=31) 0.25 mg/kg (n=14) 1 mg/kgf (n=32) 3 mg/kgf (n=33) 6 mg/kg (n=15) VLDL/Chylomicron Particles (nmol/L) 32.4c -7.6d -51.3cd -32.8cd -44.3cd -11.9 44.4 -0.74 -31.1 -31.0 LDL Particles (nmol/L) -1.3 -17.8cd -51.2cd -56.6cd -59.0cd 0.2 -12.4 -44.6cd -47.3cd -57.4cd Small LDL Particles (nmol/L) 8.5 -9.3 -57.6cd -50.9cd -68.5cd 14.3 -13.1d -42.1cd -54.6cd -58.8cd HDL Particles (umol/L) 3.9 11.1c 8.3c 9.3c 14.8cd -0.8 0.9 5.8cd 9.5cd 11.9cd VLDL Particle Size (nm) 7.8 7.5 12.1c 15.6c 12.4c 9.1c 3.9 1.4d 4.8 10.2c HDL Particle Size (nm) 0.6 0.8 1.0 1.8c 1.5c -0.5 0.3 0.8cd 1.0cd 0.3 LDL Particle Size (nm) -1.2 -0.4 1.6cd 0.3 1.1d -0.8 0.7 1.5cd 2.1cd 2.8cd a. Day 36 and Day 71 were two weeks after last dose in respective studies; b. obtained from ANCOVA model on the CFB with baseline levels as an covariant and treatment as a factor; c. p-Value for % CFB < 0.05; d. p-Value for % CFB vs Placebo < 0.05; e. Number of treated subjects with both baseline and Day 36 or Day 71 data available for analysis; f. Pooled data from Study #2 and #3.