Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C

This study will be an open label, long term extension study in subjects with atherosclerotic
cardiovascular disease (ASCVD), ASCVD-risk equivalents (eg, diabetes and familial
hypercholesterolemia), or heterozygous or homozygous familial hypercholesterolemia (HeFH or
HoFH) and elevated low density lipoprotein cholesterol (LDL-C) despite maximum tolerated dose
of LDL-C lowering therapies who have completed any of the following inclisiran Phase III
lipid lowering studies: MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-04 (ORION-10), MDCO-PCS-17-08
(ORION-11) or MDCO-PCS-17-02 (ORION-5).

Inclusion Criteria:

1. Completion of a previously qualifying Phase III lipid-lowering ORION feeder study
[MDCO-PCS-17-03 (ORION-9), MDCO-PCS-17-04 (ORION-10), MDCO-PCS-17-08 (ORION-11) or
MDCO-PCS-17-02 (ORION-5)] meaning the subject received the last dose of study drug and
completed the final study visit per applicable protocol.

2. On current lipid-lowering therapies (such as a statin and/or ezetimibe) from previous
study with no planned medication or dose change during study participation.

3. Willing and able to give informed consent before initiation of any study-related
procedures and willing to comply with all required study procedures.

Exclusion Criteria:

1. Any uncontrolled or serious disease, or any medical or surgical condition, that may
either interfere with participation in the clinical study, and/or put the subject at
significant risk [according to investigator's (or delegate's) judgment] if he/she
participates in the clinical study.

2. An underlying known disease, or surgical, physical, or medical condition that, in the
opinion of the investigator (or delegate) might interfere with interpretation of the
clinical study results.

3. Severe concomitant noncardiovascular disease that carries the risk of reducing life
expectancy to less than 3 years,

4. Active liver disease defined as any known current infectious, neoplastic, or metabolic
pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate
aminotransferase (AST), elevation >3x the upper limit of normal (ULN), or total
bilirubin (TBIL) elevation >2x ULN at the last recorded visit in the feeder study
prior to study entry visit.

5. Females who are pregnant or nursing, or who are of childbearing potential and
unwilling to use at least one method of acceptable effective contraception (eg, oral
contraceptives, barrier methods, approved contraceptive implant, long-term injectable
contraception, intrauterine device) for the entire duration of the study. Exemptions
from this criterion:

1. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual
period) and more than 55 years of age.

2. Postmenopausal women (as defined above) and less than 55 years of age with a
negative pregnancy test within 24 hours of randomization.

3. Women who are surgically sterilized at least 3 months prior to enrollment.

6. Planned use of other investigational medicinal products other than inclisiran or
devices during the course of the study.

7. Any condition that according to the investigator could interfere with the conduct of
the study, such as but not limited to:

1. Subjects who are unable to communicate or to cooperate with the investigator

2. Unable to understand the protocol requirements, instructions and study-related
restrictions, the nature, scope, and possible consequences of the study
(including subjects whose cooperation is doubtful due to drug abuse or alcohol
dependency)

3. Unlikely to comply with the protocol requirements, instructions, and
study-related restrictions (eg, uncooperative attitude, inability to return for
follow-up visits, and improbability of completing the study)

4. Have any medical or surgical condition, which in the opinion of the investigator
would put the subject at increased risk from participating in the study

5. Persons directly involved in the conduct of the study.

The above information is not intended to contain all considerations relevant to a
participant's potential participation in a clinical trial.