A multi-centre, randomised, double-blind, placebo-controlled, Phase 2 study to investigate efficacy, safety and tolerability of SLN360 in participants with elevated lipoprotein(a) at high risk of atherosclerotic cardiovascular disease events.

1. Male or female
2. Aged 18 to 80 years inclusive at screening
3. Lipoprotein(a) at screening equal to or greater than 125 nmol/L
4. At high risk of ASCVD, i.e., at least one of the following conditions:
a. Previous myocardial infarction (MI)
b. Coronary angiographic diagnosis of coronary artery disease with or without
previous MI
c. Computerised tomography/magnetic resonance imaging diagnosis of coronary
artery disease with or without previous MI
d. Previous coronary revascularisation (percutaneous coronary intervention or
coronary artery bypass graft)
e. Prior ischeamic stroke as previously confirmed by a documented brain imaging
study (e.g. computed tomography or magnetic resonance imaging brain), and
considered not to be caused by thromboembolic phenomena associated with atrial
fibrillation, valvular heart disease or mural thrombus
f. Peripheral arterial disease
g. Existing evidence of coronary artery calcium on computerised tomography
(coronary artery calcium score >=1 AU)
5. A body mass index at screening in the range 18.0 to 32.0 kg/m2, inclusive
6. Participants must be able to provide valid informed consent and to comply
with all study requirements
7. Participants receiving lipid-modifying therapy (including statins,
proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, ezetimibe)
must be on a stable, maximum tolerated regimen, according to the clinical
judgement of the Investigator, at screening (i.e., receiving therapy for a
minimum of 8 weeks) with no changes to existing regimens or introduction of new
regimens made after screening. For monoclonal antibody PCSK9 inhibitors, a
stable dose is defined as at least four doses at a consistent dose level

1. Cardiovascular disease-related: a. Acute cardiovascular event within the 12 weeks before screening (including but not limited to acute MI, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, stroke, acute limb ischaemia, limb revascularisation) b. Planned or expected cardiac surgery or coronary or other revascularisation within 12 weeks of screening or planned major non-cardiac surgery during the study period 2. Medical history: a. Renal dysfunction with estimated glomerular filtration rate less than 30 mL/min/1.73 m2 (according to the Chronic Kidney Disease Epidemiology Collaboration equation) at screening b. Acute, chronic or historical liver disease, including viral hepatitis (hepatitis A, B or C virus) at screening. Participants with positive hepatitis B virus surface antibody titre reflecting hepatitis B virus immunisation are permitted to participate c. Hepatic dysfunction based on liver function markers at screening: aspartate aminotransferase, alanine aminotransferase or total bilirubin >2 × the upper limit of the normal range (ULN) d. Established diagnosis of Gilbert syndrome e. Inherited or other bleeding disorders f. Malignancy (except non-melanoma skin cancers, cervical in situ carcinoma, breast ductal carcinoma in situ, stage 1 prostate carcinoma, or benign tumours) within the 5 years before screening g. Current or previous history of moderate to severe heart failure (New York Heart Association Functional Classification grade III or IV at screening) or last known left ventricular ejection fraction less than 30% at screening h. Ventricular tachycardia, atrial fibrillation with rapid ventricular response or supraventricular tachycardia that are not controlled by medications in the 12 weeks before screening i. Fasting triglycerides >400 mg/dL (4.5 mmol/L) at screening j. Uncontrolled hypertension at screening, defined as an average sitting systolic blood pressure > 160 mmHg or an average diastolic blood pressure >110 mmHg after a minimum of three measurements k. Type 1 diabetes mellitus or poorly controlled (glycated haemoglobin >=10% or >=86 mmol/mol) type 2 diabetes mellitus at screening l. Known active infection or major haematological, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the Investigator at screening or Day 1 3. Concomitant medication: a. Currently receiving or <12 weeks at Day 1 since receiving >200 mg/day niacin or niacin derivative drugs (e.g., niceritrol, nicomol) b. Treatment with lipid/lipoprotein apheresis within the 12 weeks before screening c. Treatment with a cholesteryl ester transfer protein inhibitor (e.g., anacetrapib, dalcetrapib, evacetrapib, obicetrapib) or lomitapide within the 52 weeks before screening d. Treatment with aspirin, clopidogrel, ticagrelor or other antiplatelet agent unless prescribed at a low maintenance dose for the purpose of cardiovascular risk reduction (i.e., aspirin up to 325 mg daily, clopidogrel 75 mg daily, ticagrelor 180 mg daily) e. Participation in another clinical trial including an investigational medicinal product within 12 weeks, or within five half-lives of that investigational medicinal product, before screening f. Any previous use of approved or experimental small interfering RNA therapy (e.g., inclisiran). NB: use of messenger RNAbased vaccines for infectious diseases is permitted g. Use of approved or experimental antisense oligonucleotide therapy within the 24 weeks before screening. NB: use of messenger RNA-based vaccines for infectious diseases is permitted h. Use of experimental Lp(a)-reducing therapy within the 52 weeks before screening i. Use of herbal or complementary medicines, dietary supplements or vitamins known to substantially influence lipid metabolism or blood lipid or lipoprotein levels (e.g., fish oil, turmeric, red yeast rice) within the 4 weeks before Day 1 4. Alcohol and illegal drugs: a. History or clinical evidence of alcohol misuse within the 26 weeks before screening b. History or clinical evidence of recreational drug use within the 26 weeks before screening 5. Other exclusions: a. Female participants of childbearing potential with a positive serum pregnancy test assessed at screening or positive urine pregnancy test on Day 1 b. Female participants of childbearing potential planning to become pregnant or breastfeed during treatment and for an additional 12 weeks after the last dose of study treatment c. Female participants of childbearing potential unwilling to use a highly effective method of contraception during treatment and for an additional 12 weeks after the last dose of study treatment d. Male participants must be surgically sterile or, if engaged in sexual relations with a female of childbearing potential, the participant must be using a highly effective contraception method from the time of signing the informed consent form until at least 12 weeks after the last dose of study treatment e. Known sensitivity to any of the products to be administered during dosing f. Likely to be unavailable to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and Investigator*s knowledge g. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Sponsor, if consulted, would pose a risk to the participant*s safety or interfere with the study evaluation, procedures or completion.