Perelman School of Medicine University of Pennsylvania

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Perelman School of Medicine University of Pennsylvania Comments on the Milano-PILOT Trial AHA Scientific Sessions Late Breaking Clinical Trials November 15, 2016 Daniel J. Rader, MD Perelman School of Medicine University of Pennsylvania

ApoA-I Milano

Nissen SE et al. JAMA 2003;290:2292–2300.

Nissen SE et al. JAMA 2003;290:2292–2300.

MILANO-PILOT Well-executed IVUS trial by world class investigators Three times the size of the original apoA-I Milano IVUS trial Convincing negative results

Reconstituted HDL products with wild-type apoA-I in clinical development CSL112 CER001

Reverse Cholesterol Transport Bile A-I A-I ABCG1 FC CE FC LCAT FC FC CE SR-BI ABCA1 Liver Macrophage

ApoA-I Milano differs from wild-type apoA-I with regard to several functions Structure

ApoA-I Milano differs from wild-type apoA-I with regard to several functions Structure Generation of pre-beta HDL

ApoA-I Milano differs from wild-type apoA-I with regard to several functions Structure Generation of pre-beta HDL Promotion of cholesterol efflux

ApoA-I Milano differs from wild-type apoA-I with regard to several functions Structure Generation of pre-beta HDL Promotion of cholesterol efflux Activation of LCAT