Assess the Safety and Tolerability of SNS851 in Study Participants

Inclusion criteria

• Able to provide written informed consent. Willing, committed, and able to return for all clinic visits and complete all protocol specified procedures.
• Healthy male or female, aged between 18 and 55 years (MAD: aged between 18 and 60 years), inclusive at screening.
• Body mass index (BMI) of greater than or equal to 18 kg/m2 and lesser than or equal to 32 kg/m2 at Screening.
• Liver fat measurements above the normal range.
• Negative human immunodeficiency virus, viral hepatitis B and C serology at Screening.
• No major changes in diet, alcohol intake, or physical activity within 4 weeks before dosing and no intention to modify during confinement or follow-up.
• No acute illness in the 4 weeks prior to check-in, as established by physical examination and medical history.
• Participant is willing to refrain from consuming caffeine and/or xanthene products (e.g., coffee, tea, chocolate, and caffeine-containing sodas, colas) for 12 hours before each study visit and while being confined to the study site.
• All participants of reproductive potential must use a highly effective contraceptive method from consent through 90 days after last dose.

Exclusion criteria

• Weight loss of more than 10% within the last 3 months prior to screening.
• Has any clinical safety laboratory result considered clinically significant by the Investigator (or designee)
• In the opinion of the PI (or designee), has evidence of other forms of known chronic liver disease
• Participants with history or pre-existing renal disease
• Relevant history (in the opinion of the PI or designee) of cardiac arrythmias including long QT syndrome, sudden cardiac death, or Torsades de Pointes and/or syncope and/or clinically significant cardiovascular event or history of uncontrolled hypertension or orthostatic hypotension within the last 6 months prior to the Screening Visit.
• QTcF interval duration > 450 msec for male or > 470 msec for female at Screening or Day 0.
• Evidence or history of clinically significant pulmonary and respiratory diseases, including any clinically significant pulmonary disease or sequelae of COVID-19 infection that may increase risk from study participation.
• Use of an investigational agent or device within 30 days or 5 half-lives since last dose of prior investigational product or device of Day 1 drug administration in this trial, whichever is longer prior to dosing or current participation in an investigational study.
• History of having received long-duration RNA-based therapies within 12 months of Day 1.
• Use of any prescription medication or concomitant medications within 14 days prior to the first dose of study drug, or use of over-the-counter medication/vitamins/supplements within 7 days prior to the first dose of study drug. Exceptions include contraception, iron supplements for participants who have ferritin between 15-30 µg/L at screening, occasional paracetamol (up to a maximum of 2 grams per day).
• Use of any vaccinations within 14 days prior to the first study drug administration.
• Use of anabolic steroids and systemic treatment with glucocorticosteroids within 3 months prior to the Screening Visit.
• History of substance dependence (within the last 12 months) or positive urine drug screen at screening or positive alcohol breath tests at screening.
• Urinary cotinine levels at screening are indicative of smoking or participant has a history of regular use of tobacco- or nicotine-containing products.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• In the opinion of the PI (or designee), has an aversion to, or has history of site reactions to Subcutaneous administrations that would make them unsuitable for inclusion in this trial.
• Has donated blood or blood products within 3 months prior to first dose administration.
• Presence or evidence of recent sunburn, scar tissue, tattoo, open sore or branding that, in the opinion of the PI or medically qualified designee, would interfere with the interpretation of skin adverse reactions at the injection site
• In the opinion of the PI (or designee), has any uncontrolled or serious disease, medical or surgical condition that may interfere with participation or data interpretation.
• Any other condition or prior therapy that in the opinion of the PI (or designee) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
• History of hypersensitivity to oligonucleotide therapeutics or injection-site reactions.