The purpose of this study is to assess the safety and tolerability of ION904.

This is a Phase 1, randomized, double-blind, placebo-controlled, single-ascending dose escalation study of ION904 in up to 72 participants. Following a Screening Period of up to 28 days, eligible healthy participants will be randomized to treatment and receive a single, subcutaneous (SC) dose of the assigned study drug. Participants will be followed for up to 13 weeks after dosing.

Inclusion Criteria:

1. Must be healthy males, or females of non-childbearing potential, aged 18 to 65 at the time of informed consent
2. Females must be either surgically sterile or post-menopausal; males must be abstinent, surgically sterile, or if engaged in sexual relations with a woman of childbearing potential, a highly effective contraceptive method must be used from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug or the healthy participant must be abstinent through this time period
3. Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) for at least 24 hours prior to study visits
4. Body mass index (BMI) requirements between 18 and 35 kg/m^2

Exclusion Criteria:

1. Clinically significant abnormalities in medical history or physical examination

2. Uncontrolled arterial hypertension

3. Active infection with human immunodeficiency virus (HIV), hepatitis C or hepatitis B or prior treatment for hepatitis C

4. Treatment with another investigational drug, biological agent, or device within 1 month of Screening

5. History of bleeding diathesis or coagulopathy

6. Regular use of alcohol within 6 months prior to screening, or use of soft drugs within 3 months prior to Screening, or hard drugs within 1 year prior to Screening, or positive urine drug screen at Screening

7. History of any severe (e.g., anaphylaxis) drug allergies

8. History of hypersensitivity to other antisense oligonucleotides (ASOs)

9. Concomitant medication restrictions: over-the-counter or prescription medications within 14 days, prior to dosing on Day 1. Accepted exceptions are:

   • Acetaminophen (paracetamol) up to 2 grams per day (g/d) or ibuprofen up to 2.4 g/day taken sporadically for analgesia
   • Thyroid hormone replacement therapy provided participant is stable on replacement therapy (and participant is euthyroid)
   • Other possible exceptions must be reviewed and acknowledged by the Investigator in consultation with Sponsor's Medical Monitor

10. Blood donation of 50 to 499 mL within 30 days of Screening or of > 499 mL within 60 days of Screening