Slide 1: Obicetrapib as an Adjunct to Stable Statin Therapy: Japan Phase 2 Study Results
Obicetrapib as an Adjunct to Stable Statin Therapy Significantly Lowers LDL-C, Non-HDL-C and Apolipoprotein B in Japanese Patients: Results from the Japan Phase 2 Study Mariko Harada-Shiba, Douglas Kling, John J Kastelein, Marc Ditmarsch, Erin Wuerdeman, Andrew Hsieh, Stephen Nicholls, Michael H Dav
Slide 2: Rationale
Rationale • Obicetrapib is a highly selective and potent CETP inhibitor, which has been developed for the treatment of dyslipidemia and CV risk • A Phase 2 study was conducted in Caucasian participants to evaluate the optimal dose of obicetrapib alone and in combination with medium-intensity statins
Slide 3: Japan Phase 2 Trial
Japan Phase 2 Trial Objective: The primary objective of this study is to evaluate the efficacy of obicetrapib, compared to placebo, in reducing serum low- density lipoprotein cholesterol (LDL-C) when taken as an adjunct to a pre-existing stable statin therapy regime Main Inclusion Criteria • Stable
Slide 4: Baseline characteristics
Baseline characteristics Placebo Obicetrapib Obicetrapib Obicetrapib 2.5 mg 5mg 10mg N=26 N=25 N=25 N=26 Mean Age (yrs) 63.3 65.8 67.8 62.5 Female % 23.1 40.0 24.0 28.4 Mean BMI (kg/m2) 25.5 25.15 25.84 26.05 Race % Asian 100 100 100 100 Statin use (%) Atorvastatin 10/20 mg 57.7 48.0 48.0 38.5 Rosuv
Slide 5: Obicetrapib significantly reduced LDL-C and ApoB
Obicetrapib significantly reduced LDL-C and ApoB LDL-C percent change from baseline ApoB percent change from baseline Placebo Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 mg Placebo Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 mg 10 10 % Change from baseline (median) % Change from baseli
Slide 6: Obicetrapib significantly reduced non-HDL-C and increased HDL-C
Obicetrapib significantly reduced non-HDL-C and increased HDL-C Non-HDL-C percent change from baseline HDL-C percent change from baseline Placebo Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 mg 10 Placebo Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 mg 190 5 % Change from baseline (media
Slide 7: Safety - AEs, SAEs and withdrawal overview
Safety - AEs, SAEs and withdrawal overview Placebo Obicetrapib Obicetrapib Obicetrapib 2.5 mg 5 mg 10 mg TEAEs (%) TEAEs, total 16 (61.5) 11 (44.0) 9 (36.0) 15 (57.7) TEAEs, related 0 0 0 0 TEAEs, severe 0 0 0 0 TESAEs TESAEs, total 0 0 1 (4.0) 0 TESAEs, related 0 0 0 0 Deaths 0 0 0 0 Withdrawal's s
Slide 8: Conclusions
Conclusions • Obicetrapib 2.5, 5 and 10 mg on top of moderate intensity dose statin therapy was well tolerated in a Japanese population with a safety profile similar to placebo • Obicetrapib 5 and 10 mg on top of moderate intensity dose statin therapy reduced median LDL-C levels with -32% and -46% f
Slide 9: Back-up
Back-up 9
Slide 10: Plasma levels of obicetrapib during and after end of therapy
Plasma levels of obicetrapib during and after end of therapy (EoT) 600 Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 502.7 506.3 500 484 Median % change from baseline 400 351 362.3 337 300 196 194.5 200 176 100 27.6 weeks 13.2 24.6 0 0 0 2 4 8 EoT +4 Obicetrapib 2.5 mg 0 176 196 194.5 13.2 Obic
Slide 11: Obicetrapib did not significantly reduce Triglycerides
Obicetrapib did not significantly reduce Triglycerides Triglycerides percent change from baseline Placebo Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 mg 10 % Change from baseline (median) 5 0 -2.5 -5 -7.0 -7.0 -10 -15 -14.0 -20 11
Slide 12: Obicetrapib significantly increased ApoE
Obicetrapib significantly increased ApoE ApoE percent change from baseline Placebo Obicetrapib 2.5 mg Obicetrapib 5 mg Obicetrapib 10 mg 50 40 36.3 % Change from baseline (mean) 31.2 30 23.5 20 10 1.2 0 -10 P<0.0001 for all dosages 12
Slide 13: LDL-C determination
LDL-C determination LDL-C was determined using the following 2 approaches: 1. LDL-C was calculated using the Friedewald equation unless triglycerides (TG) ≥400 mg/dL or LDL-C ≥ 50 mg/dL. If TG ≥ 400 mg/dL or LDL-C ≥ 50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation
Slide 14: Statistical methods I
Statistical methods I • The Intent-to-Treat (ITT) Population included all participants randomized into the study. • The Modified ITT (mITT) Population included all participants in the ITT Population who received at least 1 dose of any study drug and had a baseline value for the LDL-C assessment. • T
Slide 15: Statistical methods II
Statistical methods II • The primary efficacy analysis of the percent change from Day 1 to Day 56 in LDL-C was performed using a mixed model for repeated measures (MMRM) approach. The analysis included fixed effects for treatment, visit, and treatment-by-visit interaction, along with a covariate of