NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Key Inclusion Criteria:

1. Aged 18 to 82 years at the time of informed consent

2. Females must be non-pregnant and non-lactating, and either surgically sterile orpost-menopausal or abstinent

3. Males must be surgically sterile or, abstinent or, if engaged in sexual relationswith a woman of child-bearing potential, the participant or the participantssnon-pregnant female partner must be using a highly effective contraceptive method

4. Diagnosis of hereditary transthyretin-mediated polyneuropathy as defined by meetingall 3 of the following:

• Stage 1 or Stage 2 Familial Amyloid Polyneuropathy (FAP) or Coutinho Stage

• Documented genetic mutation in the TTR gene

• Symptoms and signs consistent with neuropathy associated with transthyretinamyloidosis, including Neuropathy Impairment Score (NIS) ≥ 10 and ≤ 130

Key Exclusion Criteria:

1. Clinically-significant (CS) abnormalities in medical history, screening laboratoryresults, physical or physical examination that would render a participantsunsuitable for inclusion, including but not limited to abnormal safety labs

2. Karnofsky performance status ≤ 50

3. Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease),including uncontrolled diabetes

4. Prior liver transplant or anticipated liver transplant within 1-yr of Screening

5. New York Heart Association (NYHA) functional classification of ≥ 3

6. Acute coronary syndrome within 6 months of screening or major surgery within 3months of Screening

7. Other types of amyloidosis

8. Have any other conditions, which, in the opinion of the Investigator or Sponsorwould make the participant unsuitable for inclusion, or could interfere with theparticipant participating in or completing the Study

9. Current treatment with any approved drug for hereditary TTR amyloidosis such asVyndaqel® / Vyndamax™ (tafamidis), Tegsedi™ (inotersen), Onpattro™ (patisiran),off-label use of diflunisal or doxycycline, and tauroursodeoxycholic acid (TUDCA).If previously treated with Vyndaqel® / Vyndamax™, diflunisal or doxycycline, andTUDCA, must have discontinued treatment for at least 2 weeks prior to Study Day 1

10. Previous treatment with Tegsedi™ (Inotersen) or Onpattro™ (patisiran), or otheroligonucleotide or RNA therapeutic (including siRNA)